Browsing by Subject "Necrosis"
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- PublicationOpen AccessAnti-leukemia activity of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines(Springer, 2019-02) Carmona-Martínez, Violeta; Guirado, Antonio; Gálvez, Jesús; García-Peñarrubia, Pilar; Martínez-Esparza Alvargonzález, María Concepción; Ruiz Alcaraz, Antonio José; Bioquímica y Biología Molecular B e Inmunología
- PublicationOpen AccessElectron probe X-ray microanalysis of cisplatininduced cell death in rat pheochromocytoma PC12 cells(Murcia: F. Hernández, 2011) Ramos, Juan M.; Arrebola, Francisco; Fernández Cervilla, Francisco J.; Crespo, Vicente; Fernández Segura, EduandoSeveral lines of evidence suggest that cisplatin-induced cell death is not always the result of apoptosis. A distinctive feature between apoptosis and necrosis is the alteration in cell volume regulation and ion homeostasis. Here we analyzed the changes in intracellular element content during cell death induced by exposure to therapeutic concentrations of cisplatin in the PC12 cell line. To quantitate Na, Cl and K content, electron probe X-ray microanalysis (EPXMA) was performed in whole freeze-dried cells. We also traced the alterations in morphological features with fluorescence and transmission electron microscopy. EPXMA demonstrated progressive derangement of the absolute intracellular Na, Cl and K contents. Cisplatin-treated cells showed two microanalytical patterns: 1) cells with alterations in elemental content typical of apoptosis, i.e., an increase in intracellular Na and a decrease in intracellular Cl and K, and 2) cells characterized by an increase in Na content and a decrease in K content, with no changes in Cl content. This intracellular profile for Na, Cl, and K was not typical of necrosis or apoptosis. Morphological analysis revealed two cellular phenotypes: 1) cells characterized by a phenotype typical of apoptosis, and 2) cells characterized by a hybrid phenotype combining variable features of apoptosis and necrosis. Taken together, our findings suggest that therapeutic concentrations of cisplatin may cause a hybrid type of cell death characterized by concurrent apoptosis and necrosis in the same individual PC12 cell.
- PublicationOpen AccessEpithelia1 integrity, cell death and cell loss in mammalian small intestine(Murcia : F. Hernández, 1999) Mayhew, T.M.; Myklebust, R.; Whybrow, A.; Jenkins, R.In recent years, the different mechanisms of epithelial cell loss which occur in mammalian and avian small intestine have been re-investigated. Information is now available for a variety of mammalian types and mechanisms can be divided into two major classes: [i] those preserving epithelial integrity by maintaining intercellular tight junctions throughout early-to-late stages of cell extrusion; and [ii] those which compromise integrity by introducing breaches in epithelial continuity. Both classes are associated with the activity andtor proximity of non-epithelia1 cells (mainly lymphocytes and mononuclear phagocytes) located in the epithelium or underlying lamina propria. Intraepithelial lymphocytes may be involved in enterocyte targetting and killing whilst lamina propria (LP) macrophages sequester cell debris. Where epithelial integrity is maintained, two types of loss can be identified. In the first (type l), complete cells are extruded into the lumen. In the second (type 2), only anucleate apical cell fragments pass into the lumen . There are two variants of type 2 loss distinguishable by the fate of the nucleated basal portions of cells. One variant (type 2a) creates large intercellular spaces extending from the preserved apical cap to the basal lamina and containing enterocyte debris for phagocytosis. The second (type 2b) involves the gradual shrinkage of individual cells (which become more electron-dense) and in situ degeneration of their nucleated subapical portions in increasingly narrower intercellular spaces between adjacent healthy enterocytes. The mechanism of removal of these fragments is unclear but may be via macrophages or surrounding enterocytes. Apoptosis has been implicated in both type 1 and type 2 extrusion. In contrast, type 3 loss involves morphological changes in enterocytes which are reminiscent of those seen in necrosis and is accompanied by breaks in epithelial continuity following cell swelling, a decrease in cell electron density and total or subtotal degradation of organelles and membranes. It ends in loss of either an abnormal cell apex (with subsequent exposure of the degraded cell contents and their spillage into the lumen) or a complete cell remnant (extruded into the lumen before total disintegration of plasma membranes).
- PublicationOpen AccessMolecular actions of nitric oxide in mesangial cells(Murcia : F. Hernández, 2000) Sandau, K.B.; Brune, B.Nitric oxide (NO) is a widely recognized mediator of physiological and pathophysiological signal transmission. Its generation through L-arginine metabolism is relevant in the mesangium of the kidney where NO is produced by constitutive and inducible NOsynthase isoenzymes. Signaling is achieved through target interactions via redox and additive chemistry. In mesangial cells (MC), the outcome of these modifications promote on one side activation of soluble guanylyl cyclase while on the other side cytotoxicity is elicited. These contrasting situations are characterized by: 1) cGMP formation and signal propagation towards myosin light chain kinase, the effector system that regulates F-actin assembly, thereby affecting reversible relaxation/contraction of mesangial cells; and 2) initiation of morphological and biochemical alterations that are reminiscent of apoptosis such as chromatin condensation, p53 or Bax accumulation as well as caspase-3 activation. Off note, NO formation with concomitant initiation of apoptosis is efficiently antagonized by the simultaneous presence of superoxide (02-). We will recall the consequences that stem from a diffusion controlled NO/02- interaction thereby redirecting the apoptotic initiating activity of either NO or 02- towards protection. The crosstalk between cell destructive and protective signaling pathways, their activation or inhibition under the modulatory influence of NO will be discussed. Here we give examples of how NO elicits physiological and pathophysiological signal transmission in rat MC.
- PublicationOpen AccessPrognostic impact of mitosis and necrosis in non-mucinous lung adenocarcinomas and correlation with IASLC grading system(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Serin, Gurdeniz; Savaş, Pınar; İşgör, İrem Şahver; Özdil, Ali; Mızrak, Ali; Veral, Ali; Nart, DenizBackground. In 2020, the International Lung Cancer Study Group (IASLC) Pathology Committee established a grading system for non-mucinous primary lung adenocarcinomas. This grading system is based on whether areas of high-grade patterns are present in more than 20% of the tumor. Parameters, such as necrosis, mitotic activity, lymphovascular invasion (LVI) and spread through air spaces (STAS), are excluded from evaluating the grading system. Methods. A total of 217 patients' lung resection materials for primary lung adenocarcinoma were re-reviewed using the IASLC grading system. Necrosis, mitotic activity, LVI status and STAS were also evaluated in the resection materials, aiming to demonstrate the relationship between these histopathological features and clinical outcome data. Results. At all stages, overall survival (OS) and recurrence-free survival (RFS) were related to grade (p=0.011 and 0.024, respectively). Additionally, patients with necrosis were associated with worse OS and RFS (p=0.002 and 0.048, respectively). When grade 2 and 3 tumors were analyzed individually, a significant relationship was found between necrosis and OS in grade 3 tumors (p=0.002). Patients with a high mitotic count (≥10/10 high-power fields) had significantly worse OS (p=0.046). The prevalence of LVI and STAS increased with grade; however, their prognostic significance has not been demonstrated. Conclusions. The new grading system provides a highly efficient prognostic classification for survival. Necrosis and high mitotic count are important prognostic parameters for survival. Additionally, necrosis is a stage-independent prognostic factor for OS in grade 3 tumors, although no effect on prognosis can be demonstrated in grade 2 tumors.
- PublicationOpen AccessThe NF-kB-mediated control of ROS and JNK signaling(Murcia : F. Hernández, 2006) Bubici, C.; Papa, S.; Pham, C.G.; Zazzeroni, F.; Franzoso, G.NF-kB/Rel transcription factors are best known for their roles in innate and adaptive immunity and inflammation. They also play a central role in promoting cell survival. This latter activity of NF-kB antagonizes programmed cell death (PCD) induced by the proinflammatory cytokine tumor necrosis factor (TNF)a and plays an important role in immunity, lymphopoiesis, osteogenesis, tumorigenesis and radioand chemo-resistance in cancer. With regard to TNFa, the NF-kB-mediated inhibition of PCD seems to involve an attenuation of the c-Jun-N-terminal kinase (JNK) cascade mediated through the induction of select downstream targets such as the caspase inhibitor XIAP, the zinc-finger protein A20, and the inhibitor of the MKK7/JNKK2 kinase, Gadd45ß/Myd118. Notably, NF- kB also blunts accumulation of reactive oxygen species (ROS), which themselves are pivotal elements for induction of PCD by TNFa, and this suppression of ROS formation mediates an additional protective activity recently ascribed to NF-kB. The antioxidant activity of NF-kB has been shown to depend upon upregulation of both Ferritin heavy chain (FHC) – a component of Ferritin, the primary iron-storage protein complex found in cells – and of the mitochondrial enzyme Mn++ superoxide dismutase (Mn-SOD). Indeed, the inductions of Mn-SOD and FHC represent another important means through which NF-kB controls proapoptotic JNK signaling triggered by TNFa. These findings might enable the development of new, more targeted approaches to treatment of diseases sustained by a deregulated activity of NF-kB, including some cancers and chronic inflammatory conditions.