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)

Apoptosis (programmed cell death) is a distinct form of controlled cell degeneration, different from necrosis. It serves multiple physiological functions, such as the control of cell numbers during development, the maintenance of tissue homeostasis and the deletion of abnormal cells. Apoptosis has unique morphological and biochemical features, especially at the nuclear level, in keeping with the idea of the active participation of the cell in its own demise. Gene regulation of apoptosis shows variability among different tissues, particularly regarding the signals that trigger cell death, but shares an effector phase highly conserved accross species. In the nervous system, genes have been identified which either i) promote apoptosis: Bax, Bcl-xS, c-fos, c-jun, p75NGFR and ICE-like proteases, or ii) block apoptosis: Bcl-2 and Bcl-xL. In addition, availability of trophic factors and expression of Trk membrane receptors allow for the fine adjustement of viable cells in each neuronal population. In some diseases, neuron loss takes place via apoptosis, whether exclusively or associated with necrosis, especially when cellular insults are of moderate intensity or death occurs in areas of the brain adjacent to necrotic foci. This has been shown in excitotoxicity, X-ray injury and hypoxia-ischemia. Activation of apoptosis occurs also in some neurodegenerative diseases. Infantile spinal muscular atrophy can be the first example of a pediatric hereditary disease where a deletion in the gene of a protein which inhibits neuron apoptosis has a pathogenic role. Last, some central nervous system infections produce abnormal activation of apoptosis.
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PMID:[Apoptosis in the nervous system]. 897 37

Infantile spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN)1 gene. We investigated the role of human (h) SMN protein on cell death in PC12 and Rat-1 cells. hSMN prolonged cell survival in PC12 cells deprived of trophic support and in Rat-1 cells induced to die by activation of the proto-oncogene c-Myc, to similar magnitude as Bcl-2 or IAP-2. While hSMN was ineffective in inhibiting apoptosis induced by ultraviolet light (UV) or etoposide treatment in proliferating PC12 or Rat-1 cells, a protective effect was observed in terminally NGF/dBcAMP-differentiated PC12 cells. hSMN inhibited the onset of apoptosis in NGF/dBcAMP-deprived or UV-treated co-differentiated PC12 cells by preventing cytochrome c release and caspase-3 activation, indicating that its effects are through suppression of the mitochondrial apoptotic pathway. Expressing hSMN deleted for exon 7 (Delta7) or for exons 6 and 7 (Delta6/7), or with the SMA point mutant Y272C, resulted in loss of survival function. Moreover, these mutants also exhibited pro-apoptotic effects in Rat-1 cells. The localization pattern of full-length hSMN in PC12 and Rat-1 cells was similar to that of endogenous SMN: granular labelling in the cytoplasm and discrete fluorescence spots in the nucleus, some of which co-localized with p80 coilin, the characteristic marker of Cajal bodies. However, cytoplasmic and nuclear aggregates were often seen with hSMNDelta7, whereas the hSMNDelta6/7 mutant showed homogenous nuclear labelling that excluded the nucleolus. Thus, our results show that the C-terminal region is critical in suppression of apoptosis by SMN.
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PMID:Involvement of survival motor neuron (SMN) protein in cell death. 1237 65