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

Myocyte apoptosis increases with age in Fischer 344 rats, but the multiple molecular events implicated in this phenomenon remain to be identified. Several defects involving Ca2+ homeostasis, pH, and the expression of p53 and genes of the Bcl-2 protein family may contribute to the activation of myocyte death. Therefore, changes in intracellular pH, cytosolic Ca2+, DNase I and DNase II were measured in myocytes isolated by enzymatic digestion from rats of different ages. Moreover, the expression of p53, Bcl-2 and Bax in these cells was determined. Measurements of intracellular pH by BCECF fluorescence at 3, 12 and 24 months showed that this parameter did not change with age: 3 months, 7.20+/-0.05; 12 months, 7.21+/-0.07; 24 months, 7.18+/-0.09. In contrast, diastolic Ca2+ determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at 3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24 months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant with age. Western blotting performed on ventricular myocytes did not detect significant changes in p53, Bax and Bcl-2 proteins with age. Similarly, immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did not change from 3 to 24 months. In conclusion, myocyte aging is characterized by an increase in diastolic calcium which may activate DNase I triggering apoptosis, independently from the expression of p53, Bax and Bcl-2 in the cells.
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PMID:Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. 951 29

Status epilepticus (SE)-induced neuronal death is morphologically necrotic and is initiated by excessive glutamate release, which activates postsynaptic N-methyl-D-aspartate (NMDA) receptors and triggers receptor-mediated calcium influx (excitotoxicity). This results in activation of intracellular proteases and neuronal nitric oxide synthase, with generation of free radicals, and damage to cellular membranes, structural proteins, and essential enzymes. Programmed cell death mechanisms, such as p53 activation, activation of cell death-promoting Bcl-2 family members, and endonuclease-induced DNA laddering, occur in SE-induced neuronal death. Caspase-independent excitotoxic mechanisms, such as NMDA-induced calpain I activation, with activation and translocation of the cell death-promoting Bcl-2 family member Bid from cytoplasm to mitochondria, and subsequent translocation of apoptosis-inducing factor and endonuclease G to nuclei (which cause large-scale and internucleosomal DNA cleavage, respectively), may be triggered by SE. Poly(ADP-ribose) polymerase-1 (PARP-1) activation and cysteinyl cathepsin and DNase II release from lysosomes may occur following SE as well, but these events await future investigation. In the future, rational combinations of central nervous system-penetrable neuroprotective agents, based on our knowledge of excitotoxic mechanisms, may be useful in refractory human SE.
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PMID:Prolonged seizures and cellular injury: understanding the connection. 1627 99