Browsing by Subject "Akt"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Publication
    Open Access
    Akt signaling and its role in postnatal neovascularization
    (Murcia : F. Hernández, 2005) Ma, F.X.; Han, Z.C.
    Postnatal neovascularization has been known to be involved in not only angiogenesis but also vasculogenesis. Several lines of evidence suggest a link between neovascularization and Akt, a family member of serine/threonine protein kinases. Akt phosphorylates endothelial NO synthase (eNOS) and thereby enhances endothelial NO synthesis and influences postnatal vessel growth. Akt signaling is activated by a variety of stimuli in endothelial cells and endothelial progenitor cells (EPCs). Activation of the Akt kinase orchestrates a number of signaling pathways potentially involved in angiogenesis. Dominant negative Akt overexpression leads to functional blocking of EPC bioactivity. Because neovascularization is implicated in the pathophysiology of a number of diseases and is becoming an important therapeutic strategy for those diseases, further dissection of the Akt pathway and elucidation of the downstream effector molecules will lead to a better understanding of postnatal neovascularization and may provide avenues for the development of novel therapeutic interventions. In this review, molecular mechanisms of Akt signal pathway will be discussed with special emphasis on its role in neovascularization.
  • Thumbnail Image
    Publication
    Open Access
    Induction of pluripotency in primordial germ cells
    (Murcia: F. Hernández, 2011) Kimura, Tohru; Nakano, Toru
    Summary. Primordial germ cells (PGCs) are the founder cells of all gametes. PGCs differentiate from pluripotent epiblasts cells by mesodermal induction signals during gastrulation. Although PGCs are unipotent cells that eventually differentiate into only sperm or oocytes, they dedifferentitate to pluripotent stem cells known as embryonic germ cells (EGCs) in vitro and give rise to testicular teratomas in vivo, which indicates a “metastable” differentiation state of PGCs. We have shown that an appropriate level of phosphoinositide-3 kinase (PI3K)/Akt signaling, balanced by positive and negative regulators, ensures the establishment of the male germ lineage by preventing its dedifferentiation. Specifically, hyper-activation of the signal leads to testicular teratomas and enhances EGC derivation efficiency. In addition, PI3K/Akt signaling promotes PGC dedifferentiation via inhibition of the tumor suppressor p53, a downstream molecule of the PI3K/Akt signal. On the other hand, Akt activation during mesodermal differentiation of embryonic stem cells (ESCs) generates PGC-like pluripotent cells, a process presumably induced through equilibrium between mesodermal differentiation signals and dedifferentiationinducing activity of Akt. The transfer of these cells to ESC culture conditions results in reversion to an ESClike state. The interconversion between ESC and PGClike cells helps us to understand the metastability of PGCs. The regulatory mechanisms of PGC dedifferentiation are discussed in comparison with those involved in the dedifferentiation of testicular stem cells, ESC pluripotency, and somatic nuclear reprogramming.
  • Thumbnail Image
    Publication
    Open Access
    Roles of long-non-coding RNAs in cancer therapy through the PI3K/Akt signalling pathway
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Ting-Wei Lee, Katherine; Gopalan, Vinod; King-yin Lam, Alfred
    The vital need for Akt in maintaining basic cellular function has highlighted its importance in carcinogenesis. Unfortunately, Akt inhibitor development outcome has remained poor, as most of them have failed to show significant clinical benefit to cancer patients during the clinical trials. Recently, a new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), which show high tissue specificity, have demonstrated great influence in cancer progression and/or cancer inhibition. As both Akt signalling pathways and lncRNAs play such innate roles in carcinogenesis, identifying the specific roles that these lncRNAs play within this pathway may represent a novel research avenue for developing Akt inhibitors with better therapeutic properties. In addition, understanding the diverse mechanism by which lncRNAs regulate gene expression can assist in deciphering the fundamentals of carcinogenesis. The focus of interest should be on the lncRNAs, which affect Akt and finding the link between lncRNAs and Akt pathways associated with carcinogenesis. LncRNAs within the Akt pathways could affect multiple pathways in a particular cancer type, which ultimately creates an intricate web of connections between the pathways. In summary, lncRNAs have tremendous potential in cancer diagnosis, assessing cancer patient prognosis and in developing new therapeutic options for patients with resistance to current cancer therapies. Thus, understanding how lncRNAs influence the Akt pathway is essential for the development of novel and effective cancer therapies.
  • Thumbnail Image
    Publication
    Open Access
    The PI3K/Akt and MAPK-ERK1/2 pathways are altered in STZ induced diabetic rat placentas
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Ozmen, Aslı; Unek, Gozde; Kipmen-Korgun, Dijle; Turkay Korgun, Emin
    Diabetic pregnancy is associated with complications such as early and late embryonic death, fetal growth disorders, placental abnormalities, and embryonal-placental metabolic disorders. Excessive apoptosis and/or changes of proliferation mechanisms are seen as a major event in the pathogenesis of diabetesinduced embryonic death, placental weight and structural anomalies. Akt and ERK1/2 proteins are important for placental and fetal development associated with cellular proliferation and differentiation mechanisms. The mechanism underlying the placental growth regulatory effects of hyperglycemia have not been elucidated. Moreover, it is still not determined how Akt and ERK1/2 proteins related proliferation and apoptosis mechanisms are influenced by Streptozotocin (STZ) induced diabetic rat placental development. The aim of this study was to investigate the expression levels and spatio-temporal immunolocalizations of Akt, p-Akt, ERK1/2 and p-ERK1/2 proteins in normal and STZ-treated diabetic rat placental development. In order to compose the diabetic group, pregnant females were injected with a single dose of 40mg/kg STZ intraperitonally seven days before their sacrifice at 12th, 14th, 16th, 18th and 20th day of their gestation. We found that maternal diabetic environment led to a decrease in ERK1/2 and Akt phosphorylation during rat placental development. It could be said that MAPK ERK1/2 and PI3K/Akt cell signaling pathways are affected from hyperglycemic conditions in rat placentas. In conclusion, hyperglycemia-induced placental and embryonal developmental abnormalities could be associated with reduction of Akt and ERK1/2 phosphorylation.