Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for activins in regulating cellular transformation is suggested by the alpha-inhibin knockout mouse in which development of gonadal tumors is associated with elevated activin levels. It was the purpose of the current study to determine whether activin had similar actions on endometrial cell lines, specifically on a well differentiated estrogen-responsive endometrial adenocarcinoma cell line (ISH) and estrogen-unresponsive cells (HEC-50) obtained from a poorly differentiated endometrial adenocarcinoma. Activin was secreted by both adenocarcinoma cell lines. Using reverse transcription-PCR, messenger RNA type I and type II activin receptor subtypes were detected in both cell lines: expression of IB and IIB was approximately three- to fourfold greater in ISH cells than in HEC-50 cells, while activin receptor IA and IIA messenger RNA levels were approximately equal in both cell lines. Activin treatment (30-300 ng/ml) caused a dose- and time-dependent inhibition of ISH cells proliferation and resulted in a significant decrease in Bcl-2 protein and mRNA levels. No difference was observed in Bax expression. There was no significant effect of activin when the cultures of ISH cells were exposed to 17beta-estradiol. In contrast, activin showed a weak, but significant, mitogenic effect on HEC-50 cells without modifications in Bax and Bcl-2 mRNA and protein levels. The results demonstrate that activin is a regulator of endometrial cancer cell growth. 17beta-Estradiol may promote resistance of estrogen-responsive endometrial cancer cells to the growth-retarding effects of activin and one of the mechanisms might be a down-regulation of the activin receptors.
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PMID:Regulation of endometrial adenocarcinoma cell proliferation by Activin-A and its modulation by 17beta-estradiol. 1208 79

Activin is a member of the transforming growth factor-beta superfamily which comprises a growing list of multifunctional proteins that function as modulators of cell proliferation, differentiation, hormone secretion and neuronal survival. This study examined the neuroprotective effect of both Activin A and B in serum withdrawal and oxidative stress apoptotic cellular models and investigated the expression of pro- and anti-apoptotic proteins, which may account for the mechanism of Activin-induced neuroprotection. Here, we report that recombinant Activin A and B are neuroprotective against serum deprivation- and toxin- [either the parkinsonism-inducing neurotoxin, 6-hydroxydopamine (6-OHDA) or the peroxynitrite donor, 3-(4-morpholinyl) sydnonimine hydrochloride (SIN-1)] induced neuronal death in human SH-SY5Y neuroblastoma cells. Furthermore, we demonstrate for the first time that transient transfection with Activin betaA or betaB significantly protect SH-SY5Y and rat pheochromocytoma PC12 cells against serum withdrawal-induced apoptosis. This survival effect is mediated by the Bcl-2 family members and involves inhibition of caspase-3 activation; reduction of cleaved poly-ADP ribose polymerase and phosphorylated H2A.X protein levels and elevation of tyrosine hydroxylase expression. These results indicate that both Activin-A and -B share the potential to induce neuroprotective activity and thus may have positive impact on aging and neurodegenerative diseases to retard the accelerated rate of neuronal degeneration.
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PMID:The neuroprotective effect of Activin A and B: implication for neurodegenerative diseases. 1768 Sep 97

Normal testicular function is dependent upon hormones acting through endocrine and paracrine pathways both in vivo and in vitro. Sertoli cells provide factors necessary for the successful progression of spermatogonia into spermatozoa. Sertoli cells have receptors for follicle stimulating hormone (FSH) and testosterone which are the main hormonal regulators of spermatogenesis. Hormones such as testosterone, FSH and luteinizing hormone (LH) are known to influence the germ cell fate. Their removal induces germ cell apoptosis. Proteins of the Bcl-2 family provide one signaling pathway which appears to be essential for male germ cell homeostasis. In addition to paracrine signals, germ cells also depend upon signals derived from Sertoli by direct membrane contact. Somatostatin is a regulatory peptide playing a role in the regulation of the proliferation of the male gametes. Activin A, follistatin and FSH play a role in germ cell maturation during the period when gonocytes resume mitosis to form the spermatogonial stem cells and differentiating germ cell populations. In vitro cultures systems have provided evidence that spermatogonia in advance stage of differentiation have specific regulatory mechanisms that control their fate. This review article provides an overview of the literature concerning the hormonal pathways regulating spermatogenesis.
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PMID:Hormonal regulation of spermatogenesis and spermiogenesis. 1840 Apr 89

Activin has a wide variety of biological functions, including the regulation of cell proliferation and inhibition of tumor cells. We have studied whether activin regulates apoptosis by investigating the effects of activin A on cell proliferation, cell cycle, apoptosis, apoptosis-related gene expression, and caspase activity in SNU-16 cells. Activin A significantly inhibited DNA synthesis and growth suppression in a time-dependent manner in SNU-16 cells. Apoptosis fraction was increased at cell cycle with an accompanying DNA fragmentation. Activin A resulted in a significant time-dependent decrease in Bcl-2 mRNA levels and increase in caspase-3 mRNA levels in SNU-16 cells. No significant difference was observed in Bax mRNA levels. Exposure of cells to activin A induced caspase-3, -8 and -9 activation in SNU-16 cells. Furthermore, co-treatment of activin with the pan-caspase inhibitor Z-VAD-FMK, caspase-3 inhibitor Z-DEVE-FMK, caspase-8 inhibitor Z-IETD-FMK, and caspase-9-inhibitor Z-LEHD-FMK blocked apoptosis of SNU-16 cells. Taken together, our results revealed that activin inhibits the growth of SNU-16 cells by inducing apoptosis through caspase activation.
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PMID:Cell growth regulation through apoptosis by activin in human gastric cancer SNU-16 cell lines. 1914 27

Spermatogenesis is contingent upon hormones and growth factors acting through endocrine and paracrine pathways either in vivo or in vitro. Sertoli cells (SCs) furnish essential factors for the successful advancement of spermatogenesis and spermiogenesis. Moreover, receptors for follicle stimulating hormone (FSH) and testosterone, which are the main hormonal regulators of spermatogenesis, are identified on SCs. Testosterone, FSH and luteinizing hormone are known to determine the destiny of germ cells and in their absence germ cells undergo apoptosis. Bcl-2 family proteins determine one signaling pathway which seems to be crucial for the homeostasis of male gametes. In addition to paracrine signals, germ cell development also relies on signals generated by SCs via direct membrane contact. The regulatory peptide somatostatin has an important role in the regulation of the proliferation of the male germ cells. Activin A, follistatin and FSH control germ cell development. In vitro culture systems have provided initial evidence supporting the achievement of the completion of the first and second male meiotic division in vitro. This review article provides an overview of the literature regarding the hormonal pathways governing spermatogenesis and spermiogenesis.
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PMID:The Sertoli cell as the orchestra conductor of spermatogenesis: spermatogenic cells dance to the tune of testosterone. 2673 53