DigitalUM :: Browsing by Subject "Apoptosis"

Browsing by Subject "Apoptosis"

Now showing 1 - 20 of 173

Open Access
55-Azacytidine (5Az) inducesapoptosis in PC12 cells: a model for 5Az-induced apoptosis in developing neuronal cells
(Murcia : F. Hernández, 1997) Hossain, M.M.; Nakayama, Hiroyuki; Takashima, A.; Goto, N.; Doi, K.
Our previous in vivo and in vitro studies showed that 5-azacytidine (5Az), a cytidine analog, induced apoptosis in developing neuronal cells in mice. To develop a system in which the precise molecular mechanism of 5Az-induced apoptosis in developing neuronal cells could be elucidated, we carried out the present study with PC12 cells. These cells are derived from a rat pheochromocytoma and extrude neurites in response to nerve growth factor (NGF). Light microscopy showed dose-dependent pyknotic and karyorrhectic changes in undifferentiated PC12 cells. Although they were less sensitive to 5Az, NGF-treated differentiated cells showed the same changes. Analysis by the TUNEL method (an in situ method for the detection of apoptosis) showed positive signals in the pyknotic and fragmented nuclei of these cells. Transmission electron microscopy revealed margination, segmentation, and condensation of nuclear chromatin, cell body shrinkage, and cytoplasmic vacuolization. Scanning electron microscopy demonstrated bleb formation on the cell surface. These pathomorphological changes are typical of apoptosis. 5Az seemed to affect cells that were in the proliferative stage; when the cells were terminally differentiated, their sensitivity to 5Az appeared to decline. PC12 cells could be used as a pathomorphological and biochemical model for studies of 5Az-induced neuronal cell apoptosis at the molecular and genetic level.
Open Access
A salvianolic acid 8-rich fraction of Sa/via miltiorrhiza induces neointimal cell apoptosis in rabbit angioplasty model
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Hung, H.-H.; Chen, Y.-L.; Lin, S.-J.; Yang, S.-P.; Shih, C.-C.; Shiao, M.-S.; Chang, C.-H.
Apoptosis has been suggested to participate in stabilizing cell number in restenosis. Salvia miltiorrhiza (SM) Bunge which is a Chinese herb widely used for the treatment of cardiovascular disorders contains a potent antioxidant, Salvianolic ac id B. To determ ine whether the antioxidant affects vascular apoptosis, the present study examined the frequency of apoptotic cell death in atherosclerotic plaques and in restenotic lesions of cholesterol-fed rabbits. New Zealand White rabbits were treated with a normal diet (normal), a 2% cholesterol diet (HC), a 2% cholesterol diet and endothe lial denudation (HC-ED), a 2 % cholesterol diet with 5% water-soluble extract of SM (4.8 glKg B. W./day) and endothelial denudation (HCED-SM), or with a 2% cholesterol diet containing probucol (0.6 glkg B.W./day) and endothelial denudation (HC-ED-probucol). Apoptosis and associated cell types were examined in serial paraffin sections by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry. The expression of p53, an apoptosis-related protein, was also examined. Apoptosis was mainly detected in the neointima of the three gro ups with endothe lial denudation. The percentage of apoptotic cells in SMtreated group (68.5±5.9%) was significantly higher than that of normal (0 %), HC (1.9±1.2 %), HC-ED (46.1±5.4%), and probucol-treated (32.8±3.9%) groups. The SM treatment markedly reduced the thickness of the neointima which was mainly composed of smooth muscle cells with few macrophages. In accordance with the apoptotic cell counts, positive immunoreactivity for p53 was observed in restenotic lesions from HC-ED, SM-treated and probucol-treated groups but not in the intima of the other two groups. These results suggest that the treatment with salvianolic acid B-rich fraction of SM induces apoptosis in neointima which in turn may help prevent the neointimal thickening.
Open Access
A truncated isoform of the PP2A B56g regulatory subunit reduces irradiation-induced Mdm2 phosphorylation and could contribute to metastatic melanoma cell radioresistance
(Murcia : F. Hernández, 2004) Koma, Y.-i.; Ito, A.; Watabe, K.; Kimura, S. H.; Kitamura, Y.
F10, a subline of the B16 mouse melanoma cell line, is itself the parent of the more metastatic BL6 line. BL6 cells differ from F10 cells by an alteration of the gene encoding the B56g regulatory subunit of protein phosphatase 2A (PP2A), which results in mRNA encoding a truncated variant of the subunit (Dg1). Expression of Dg1 protein is detectable only when BL6 cells are transplanted into mice and then g-irradiated. Recently, B56g subunit-containing PP2A holoenzymes have shown to dephosphorylate Mdm2, a negative regulator of p53. Thus, we assessed whether the expression of Dg1 affects irradiation-induced phosphorylation of Mdm2 and radioresistance of melanoma cells by perturbing the regulation of p53. Western blot analyses revealed that irradiated COS-7 and NIH3T3 cells stably expressing Dg1 showed significantly less irradiation-induced Mdm2 phosphorylation. Mdm2 phosphorylation reduces the ability of Mdm2 to target p53 for degradation, which probably explained why p53 protein levels in NIH3T3 cells expressing Dg1 were not significantly elevated by irradiation, unlike in wild-type cells. This was also true for F10 cells transfected with Dg1 (F10Dg1) when the cells expressed Dg1 after being irradiated in vivo. p53 mRNA levels in irradiated wild-type and Dg1-expressing cells were both only slightly elevated, suggesting that Mdm2 regulates p53 levels by a post-transcriptional mechanism. p53-mediated induction of the pro-apoptotic gene encoding Bax was also significantly lower in F10Dg1 cells irradiated in vivo. Moreover, F10Dg1 and BL6 cells were less apoptotic than F10 cells when the cells were irradiated in vivo. The p53 in F10 cells appears to be as functional as that in NIH3T3 cells because irradiation-induced expression of p53-target genes was comparable in both cells. Collectively, Dg1 appears to reduce irradiation-induced Mdm2 phosphorylation, which then blocks irradiation-stimulated p53 accumulation. Defects, such as Dg1, in PP2A may thus contribute to melanoma cell radioresistance.
Open Access
Abnormal distribution of CD45 isoforms expressed by CD4+ and CD8+ T cells in rheumatoid arthritis
(Murcia : F. Hernández, 2000) Mamoune, A.; Durand, V.; Le Goff, P.; Pennec, Y.L.; Youinou, P.; Le Corre, R.
CD45RO+ T cells are referred to as memory or helper-inducer while CD45RA+ T cells are regarded as naive or suppressor-inducer T cells. The former population predominates in the peripheral blood and even more in the synovial fluid of patients with rheumatoid arthritis, to the expense of the latter population. Within the CD45RB+ compartment, there appears to be more of the fully-differentiated than of the early-differentiated CD4+ T cells. In spite of the fact that these lymphocytes are close to undergoing apoptosis, this programmed cell death is inhibited in the rheumatoid synovium.
Open Access
ABRACL upregulated by transcription factor CBX4 promotes proliferation and migration and inhibits the apoptosis of gastric cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Guo, Kai; Gao, Xiao
Background. Gastric cancer (GC) is a predominant health concern in many countries. Actin-binding Rho activating C-terminal-like (ABRACL) belongs to a new family of low molecular weight proteins and has been implicated in cancers. This study was implemented to elucidate the role and mechanism of ABRACL in GC. Methods. The mRNA and protein expression of ABRACL and CBX4 in human gastric epithelium cell line GES-1 and GC cell lines was assessed with RT-qPCR and western blot. The transfection efficacy of sh-ABRACL, oe-CBX4, and sh-CBX4 was examined with RT-qPCR and western blot. AGS cell proliferation, migration, and invasion were evaluated using CCK-8, colony formation assay, wound healing, and Transwell assays, respectively. With western blot analysis, flow cytometry, and caspase-3 assay kits, the expressions of MMP2 and MMP9, cell apoptosis, and caspase-3 activity were estimated. Western blot was adopted to estimate the contents of apoptosis-related proteins. Luciferase reporter and chromatin immunoprecipitation (ChIP) were applied to verify the interaction between ABRACL and CBX4. Results. The expression of ABRACL and CBX4 was increased in GC tissues and cells. After interfering with ABRACL, the proliferation, migration, and invasion of GC cells were inhibited while apoptosis was promoted. We also discovered that CBX4 could bind to ABRACL and transcriptionally regulate ABRACL expression in AGS cells. Rescue experiments revealed that CBX4 overexpression partially reversed the regulatory effects of ABRACL silencing on the proliferation, migration, invasion, and apoptosis of GC cells. Conclusion. Collectively, ABRACL transcriptionally upregulated by CBX4 promoted the malignant progression of GC.
Open Access
Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Anghel, N.; Herman, H.; Balta, C.; Rosu, M.; Stan, M.S.; Nita, D.; Ivan, A.; Galajda, Z.; Ardelean, A.; Dinischiotu, A.; Hermenean, A.
Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i.p.) injected with a single dose of 15 mg/kg DOX. DOXtreated rats were characterized by decreased body and heart weights, elevated levels of creatine kinase (CKMB) and lactate dehydrogenase (LDH) activities compared to controls. Biochemical analyses on RV tissue revealed that the level of malondialdehyde (MDA) was significant increased (p<0.05) and activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX) antioxidant enzymes were decreased by 13%, 27% and 18%, respectively, compared to control. Histopathogical and electron microscopic studies revealed DOX-induced damage in both ventricles and an increase of interstitial collagen fibers compared to controls (p<0.001), whereas immunohistochemical analysis showed weak and irregular desmin expression. Furthermore, mitochondrion-induced apoptotic pathways were also activated in both ventricles, as reflected by the up-regulation of Bax/Bcl-2 mRNA expression ratio (p<0.001) and increase of Bax and caspase-3 protein expression, as well as by the significant elevation of TUNEL positive nuclei, compared to controls (p<0.001). The results showed that DOX exerted RV toxic effects at the same time as those reported in the LV, which might be mediated through the mitochondrial-dependent apoptosis.
Open Access
Aging and uterine serous carcinoma
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Hachisuga, Toru
Uterine serous carcinoma (USC) is closely associated with advanced age in patients. The p53 signature (p53S) is considered the earliest indication for the presence of carcinogenesis of USC. Based on our previous studies, the presence of p53Ss have almost always been found in elderly women and are suspected of being responsible for the imbalance between the proliferation and apoptosis of endometrial epithelial cells with advanced age. We have summarized the current state of knowledge regarding the association between age and cancer and propose an age-related type of endometrial cancer instead of Type II estrogenindependent endometrial cancer.
Open Access
Albiflorin relieves cerebral ischemia-reperfusion injury by activating Nrf2/HO-1 pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhu, Fei; Xiong, Jianzhong; Yi, Fei; Luo, Ermin; Huang, Chun; Li, Runying
Our work aims to investigate the functions of a natural compound, Albiflorin (AF) in cerebral ischemia-reperfusion (IR) injury. The cerebral IR models were established by OGD/R in PC12 cells and MCAO/IR in rats. The cells in a glucose-free medium were placed in an anaerobic chamber containing 95% N2 and 5% CO2 for 3h at 37°C, returned to a normal medium, and incubated for 24h to accomplish OGD/R. Focal cerebral ischemia was conducted by thread occlusion of the right middle cerebral artery for 2h followed by 24h reperfusion in rats. CCK-8 assay indicated that AF had no toxicity to PC12 cells. Flow cytometry, Western blot, or TUNEL showed that AF treatment reduced apoptosis of cells or rat brain tissues. qRT-PCR and ELISA showed that AF decreased IL-1β, IL-6, and TNF-α levels in vitro and in vivo. Elevated levels of MDA, SOD, and ROS induced by IR injury were mitigated by AF in vitro and in vivo. HE and TTC staining revealed that AF ameliorated pathological injury in MCAO/IR rats. Western blot showed that Nrf2, NQO1, and HO-1 expression was activated by AF, and ML385 treatment suppressed the inhibition effects of AF in cerebral IR injury models. Overall, AF alleviates cerebral IR injury via regulating the Nrf2/HO-1 pathway.
Open Access
Angiotensin AT1 receptor inhibition-induced apoptosis by RhoA GTPase activation and pERK1/2 signaling pathways in neonatal obstructive nephropathy
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Bocanegra, Victoria; Rinaldi Tosi, Martín; Gil Lorenzo, Andrea; Cacciamani, Valeria; Manucha, Walter; Fornés, Miguel; Vallés, Patricia C.
Intrarenal renin-Angiotensin system (RAS) activity is increased during early development and is further enhanced by unilateral ureteral obstruction (UUO). We studied the involvement of mitogen-activated protein (MAP) kinase members and the RhoA GTPase signaling pathways on the regulation of renal cell response after AT1 Angiotensin II receptor inhibition in obstruction. Neonatal rats subjected to sham operation or complete UUO within the first 48 hours of life received saline vehicle, Losartan (AT1 inhibitor), or PD-123319 (AT2 inhibitor) during the first 14 days of life. Cortex tubular epithelial cell apoptotic response was shown by TUNEL and confirmed by electron microscopy associated with mitochondrial signaling pathway through the increased proapoptotic ratio Bax/BcL-2, and consequently increased caspase 3 expression and activity in obstructed kidney before and after Type 1 (AT1) receptor blockade. Non injury of contralateral kidney was shown. The convergence of two independent signal pathways, the RhoA GTPase and pERK and concurrent inhibition of JNK MAP kinase, were required for the apoptotic response in 14 day kidney obstructed tubular cells either with or without Losartan treatment. Absence of increased AT2 protein expression after AT1 receptor inhibition on day 14 of obstruction was shown. Selective AngiotensinAT2-receptor inhibition with PD-123319 had no protective effect on the renal response to complete 14 day UUO. We suggest a role of both RhoA GTPase activation and the opposing actions of the ERK and JNK-MAP kinase signaling pathways as events involved in tubular cell apoptosis regulation in neonatal UUO. The selective AT1-receptor inhibition had no effect on the renal cellular response in the kidney subjected to UUO for 14 days.
Open Access
Animal models for retinitis pigmentosa induced by MNU; disease progression, mechanisms and therapeutic trials
(Murcia : F. Hernández, 2010) Tsubura, A.; Yoshizawa, K.; Kuwata, M.; Uehara, N.
Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases in humans characterized by loss of photoreceptor cells leading to visual disturbance and eventually to blindness. A single systemic administration of N-methyl-N-nitrosourea (MNU) causes retinal degeneration in various animal species. The retinal degeneration is highly reproducible, and the photoreceptor cell loss occurs within seven days after MNU administration via apoptosis resembling human RP. Here, we describe the disease progression, disease mechanisms, and therapeutic trials of MNUinduced retinal degeneration.
Open Access
Annexin-A1 short peptide alleviates septic myocardial injury by upregulating SIRT3 and inhibiting myocardial cell apoptosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Qin, Song; Ren, Yingcong; Feng, Banghai; Wang, Xiaoqin; Liu, Junya; Zheng, Jie; Li, Kang; Mei, Hong; Dai, Qiuyu; Yu, Hong; Fu, Xiaoyun
Septic myocardial injury is a common complication of severe sepsis, which occurs in about 50% of cases. Patients with this disease may experience varying degrees of myocardial damage. Annexin-A1 short peptide (ANXA1sp), with a molecular structure of Ac-Gln-Ala-Tyr, has been reported to exert an organ protective effect in the perioperative period by modulating sirtuin-3 (SIRT3). Whether it possesses protective activity against sepsis-induced cardio-myopathy is worthy of study. This study aimed to investigate whether ANXA1sp exerts its anti-apoptotic effect in septic myocardial injury in vitro and in vivo via regulating SIRT3. In this study, we established in vivo and in vivo models of septic myocardial injury based on C57BL/6 mice and primary cardiomyocytes by lipopolysaccharide (LPS) induction. Results showed that ANXA1sp pretreatment enhanced the seven-day survival rate, improved left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), and cardiac output (CO), and reduced the levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Western blotting results revealed that ANXA1sp significantly increased the expression of SIRT3, Bcl-2, and downregulated Bax expression. TUNEL staining and flow cytometry results showed that ANXA1sp could attenuate the apoptosis rate of cardiomyocytes, whereas this anti-apoptotic effect was significantly attenuated after SIRT3 knockout. To sum up, ANXA1sp can alleviate LPS-induced myocardial injury by reducing myocardial apoptosis via SIRT3 upregulation.
Open Access
Anti-apoptotic effects and mechanisms of salvianolic acid A on cardiomyocytes in ischemia-reperfusion injury
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Qian, Wei; Wang, Zilong; Xu, Tongda; Li, Dongye
Prompt myocardial reperfusion during acute myocardial infarction by fibrinolytic therapy, percutaneous coronary intervention, or coronary artery bypass grafting limits the affected area and improves prognosis. However, reperfusion itself can cause cardiomyocyte damage and decrease treatment efficacy. No treatments that effectively prevent myocardial ischemia/reperfusion (I/R) injury are currently available, and are therefore the focus of ongoing research. Salvianolic acid A (SAA), the active ingredient of the traditional Chinese herbal remedy Salvia miltiorrhiza, has anti-thrombotic activity, anti-inflammatory, and anticancer activity; regulates blood lipids and provides hepatic and neural protection. Recent studies demonstrated that SAA inhibits cardiomyocyte apoptosis in response to I/R by the PI3K/Akt, GSK-3β, JNK, and ERK1/2 pathways, and by JNK-ERK1/2 crosstalk. The mechanisms for SAA attenuating cardiomyocytes apoptosis during I/R injury through the P38 MAPK, caspase, JAK/STAT, NF-κB and LOX-1 signaling pathways need further illustration. There may be potential crosstalks between PI3K/Akt and JNK, and Akt/GSK-3β and ERK1/2 in the process of SAA against I/R-incuced cardiomyocytes apoptosis. This review summarizes the recent evidence of the anti-apoptotic effects and mechanisms of SAA against myocardial I/R injury and discusses the basis of potential clinical applications of SAA.
Open Access
Anti-leukemia activity of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines
(Springer, 2019-02) Ruiz-Alcaraz, Antonio J.; Carmona-Martínez, Violeta; Guirado, Antonio; Gálvez, Jesús; Martínez-Esparza, M.; García-Peñarrubia, Pilar; Bioquímica y Biología Molecular B e Inmunología
Open Access
Antitumor Activity of Rosmarinic Acid-Loaded Silk Fibroin Nanoparticles on HeLa and MCF-7 Cells
(MDPI, 2021-09-18) Fuster, M. G.; Carissimi, G.; Montalbán, M. G.; Víllora, G.; Ingeniería Química; Facultad de Química
Rosmarinic acid (RA), one of the most important polyphenol-based antioxidants, has drawn increasing attention because of its remarkable bioactive properties, including anti-inflammatory, anticancer and antibacterial activities. The aim of this study was to synthesize and characterize RA-loaded silk fibroin nanoparticles (RA-SFNs) in terms of their physical–chemical features and composition, and to investigate their antitumor activity against human cervical carcinoma and breast cancer cell lines (HeLa and MCF-7). Compared with the free form, RA bioavailability was enhanced when the drug was adsorbed onto the surface of the silk fibroin nanoparticles (SFNs). The resulting particle diameter was 255 nm, with a polydispersity index of 0.187, and the Z-potential was 􀀀17 mV. The drug loading content of the RA-SFNs was 9.4 wt.%. Evaluation of the in vitro drug release of RA from RA-SFNs pointed to a rapid release in physiological conditions (50% of the total drug content was released in 0.5 h). Unloaded SFNs exhibited good biocompatibility, with no significant cytotoxicity observed during the first 48 h against HeLa and MCF-7 cancer cells. In contrast, cell death increased in a concentration-dependent manner after treatment with RA-SFNs, reaching an IC50 value of 1.568 and 1.377 mg/mL on HeLa and MCF-7, respectively. For both cell lines, the IC50 of free RA was higher. The cellular uptake of the nanoparticles studied was increased when RA was loaded on them. The cell cycle and apoptosis studies revealed that RA-SFNs inhibit cell proliferation and induce apoptosis on HeLa and MCF-7 cell lines. It is concluded, therefore, that the RA delivery platform based on SFNs improves the antitumor potential of RA in the case of the above cancers.
Open Access
Antitumor activity of rosmarinic acid-loaded silk fibroin nanoparticles on HeLa and MCF-7 cells
(MDPI, 2021-09-18) Fuster, Marta G.; Carissimi, Gúzmán; García Montalbán, Mercedes; Víllora, Gloria; Departamento de Ingeniería Química
Rosmarinic acid (RA), one of the most important polyphenol-based antioxidants, has drawn increasing attention because of its remarkable bioactive properties, including anti-inflammatory, anticancer and antibacterial activities. The aim of this study was to synthesize and characterize RA-loaded silk fibroin nanoparticles (RA-SFNs) in terms of their physical–chemical features and composition, and to investigate their antitumor activity against human cervical carcinoma and breast cancer cell lines (HeLa and MCF-7). Compared with the free form, RA bioavailability was enhanced when the drug was adsorbed onto the surface of the silk fibroin nanoparticles (SFNs). The resulting particle diameter was 255 nm, with a polydispersity index of 0.187, and the Z-potential was −17 mV. The drug loading content of the RA-SFNs was 9.4 wt.%. Evaluation of the in vitro drug release of RA from RA-SFNs pointed to a rapid release in physiological conditions (50% of the total drug content was released in 0.5 h). Unloaded SFNs exhibited good biocompatibility, with no significant cytotoxicity observed during the first 48 h against HeLa and MCF-7 cancer cells. In contrast, cell death increased in a concentration-dependent manner after treatment with RA-SFNs, reaching an IC50 value of 1.568 and 1.377 mg/mL on HeLa and MCF-7, respectively. For both cell lines, the IC50 of free RA was higher. The cellular uptake of the nanoparticles studied was increased when RA was loaded on them. The cell cycle and apoptosis studies revealed that RA-SFNs inhibit cell proliferation and induce apoptosis on HeLa and MCF-7 cell lines. It is concluded, therefore, that the RA delivery platform based on SFNs improves the antitumor potential of RA in the case of the above cancers.
Open Access
Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease
(Murcia : F. Hernández, 1997) Anglade, P.; Vyas, S.; Javoy-Agid, F.; Herrero Ezquerro, María Trinidad; Michel, P.P.; Marquez, J.; Mouatt-Prigent, A.; Ruberg, M.; Hirsch, E.C.; Agid, Y.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss confined mostly to dopaminergic neurons of the substantia nigra. Several factors, including oxidative stress, and decreased activity of complex 1 mitochondrial respiratory chain, are involved in the degenerative process. Yet, the underlying mechanisms leading to dopaminergic cell loss remain elusive. Morphological assessrnent for different modes of cell death: apoptosis, necrosis or autophagic degeneration, can contribute significantly to the understanding of this neurona1 loss. Ultrastructural examination revealed characteristics of apoptosis and autophagic degeneration in melanized neurons of the substantia nigra in PD patients. The results suggest that even at the final stage of the disease, the dopaminergic neurons are undergoing active process of cell death.
Open Access
Apoptosis and proliferation of the prostate cells in men with benign prostatic hyperplasia and concomitant metabolic disorders
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Rył, Aleksandra; Rotter, Iwona; Kram, Andrzej; Teresiński, Leszek; Słojewski, Marcin; Dołęgowska, Barbara; Lubkowska, Anna; Piasecka, Małgorzata; Laszczyńska, Maria
Introduction. Apoptosis and proliferation of prostate cells are associated with both physiological increase and hyperplasia of the prostate. The aim of this study was to determine the contribution of metabolic syndrome to the processes of apoptosis and proliferation in gland epithelial cells and prostatic stromal cells in men with BPH. Materials and methods. The study involved 151 men, aged 52-89 years, receiving pharmacological treatment for BPH. The men were divided into two groups: those with and those without metabolic syndrome. The serum levels of the parameters were determined. Reactions for the identification of apoptosis (TUNEL) and proliferation (PCNA) in cells were also performed. Results. The relationships between the number of TUNEL(+) and PCNA(+) cells and metabolic syndrome were not observed. It was found that the total number of TUNEL(+) cells in the prostate stroma correlated negatively with the levels of highdensity lipoprotein and insulin-like growth factor-1. The analysis of the correlations in BPH patients with and without metabolic syndrome demonstrated that the only parameter correlating with the number of PCNA(+) cells in the prostate stroma was insulin resistance. Conclusion. Metabolic syndrome in patients with BPH had no impact on the number of TUNEL(+) and PCNA(+) cells in the prostate gland. However, the disturbed levels of metabolic parameters, and deviations of anthropometric parameters from normal may influence the number of apoptotic and proliferating cells.
Open Access
Apoptosis in adenoma and early adenocarcinoma of the colon
(Murcia : F. Hernández, 1998) Yamamoto, T.; Igarashi, N.; Kato, Y.; Kobayashi, M.; Kawakami, M.
Twenty-six specimens of tubular adenoma and 7 specimens of adenocarcinoma in adenoma of the colon were examined to evaluate apoptosis between adenoma and early adenocarcinoma. Cell proliferation and cell death seemed to be balanced in adenoma with mild and moderate atypia, but unbalanced in adenoma with severe atypia and cancer. Apoptosis was considered to be suppressed at cancer in some cases. However, a number of apoptosis increased at cancer in other cases. Necrosis was seen only in cancer areas. The ratio of cells simultaneously stained by anti-Ki-67 antibody (MIB-1) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) tended to be high from adenoma with moderate atypia to cancer, suggesting the unstableness of DNA. It is possible that cancer cells having highly unstable DNA easily underwent apoptosis as well as necrosis, accidentally. The p53 protein was positive only in cancer areas of three cases. One of these three cases showed decreased apoptosis in a cancer area, but the other two cases showed increased apoptosis. Furthermore, certain numbers of cancer cells were double-stained by p53 immunohistochemistry and TUNEL. These results suggest that the p53 protein may contribute to suppress apoptosis in the last stage of carcinogenesis of the colonic adenocarcinoma, but other factors including extrinsic stimulation may cause apoptosis despite the mutation of p53 protein.
Open Access
Apoptosis in cancer: therapeutic implications
(Murcia : F. Hernández, 2000) Negoescu, A.
This review outlines the principal limitations of the mechanisms of active cell death (ACD, apoptosis) as the basis of tumorigenesis and the rationale of almost all therapies of malignancy. The concentration of cancer therapy in the directon of ACD induction is presented as both the result of progressive understanding of the mechanisms of apoptosis and that of the favourable tumor environment for ACD signal transmission. The latter property induces the by-stander killing of cancer cells, a fundamental mechanism because efficiency of all known methods of cancer treatment is far below 100%. Finally, recent results and hypotheses regarding cancer gene therapy based on final inductors of apoptosis and endogeneous ACD inhibitors in tumors are evaluated.
Open Access
Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging
(Murcia : F. Hernández, 1997) Anglade, P.; Vyas, S.; Hirsch, E.C.; Agid, Y.
Morphological and biochemical alterations have been described in neurons of the aged human brain. However, the cell death process associated with neuronal senescence remains to be elucidated. Apoptosis and autophagic degeneration, two modes of programmed cell death described in embryogenesis and tissue renewal in adult, have been observed in nigral dopaminergic neurons in patients with Parkinson's disease. In the present study, we made the hypothesis that programmed cell death may be also involved in the death of nigral dopaminergic neurons occurring during aging. Cell death types were defined by morphological criteria identified at subcellular level. We thus performed an ultrastructural analysis in order to search for apoptotic and autophagic features in melanized neurons of the substantia nigra in four normal aged subjects. Morphological characteristics of apoptosis, such as contact loss with surrounding tissues, cell shnnkage and chromatin condensation, were found in 2% of the total number of melanized neurons analyzed. Although endoplasmic reticulum appeared normal, mitochondria were markedly shrunken. Fragments of melanized neurons were found in glial cells. Autophagic degeneration or necrosis were not detected in melanized neurons. Signs of oxidative stress, such as vacuolation of mitochondria, were obsewed in melanized neurons devoid of apoptotic features. These findings demonstrate that apoptosis is involved in cell death of nigral dopaminergic neurons during normal aging. Since morphological abnormalities found in this study, such as marked mitochondrial shrinkage in apoptotic neurons, were not observed in patients with Parkinson's disease, the mechanisms underlying apoptosis may be different in aging and pathology.