Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing evidence indicates that caspase activation and apoptosis are associated with a variety of neurodegenerative disorders, including Alzheimer's disease. We reported that anesthetic isoflurane can induce apoptosis, alter processing of the amyloid precursor protein (APP), and increase amyloid-beta protein (Abeta) generation. However, the mechanism by which isoflurane induces apoptosis is primarily unknown. We therefore set out to assess effects of extracellular calcium concentration on isoflurane-induced caspase-3 activation in H4 human neuroglioma cells stably transfected to express human full-length APP (H4-APP cells). In addition, we tested effects of RNA interference (RNAi) silencing of IP(3) receptor, NMDA receptor, and endoplasmic reticulum (ER) calcium pump, sacro-/ER calcium ATPase (SERCA1). Finally, we examined the effects of the NMDA receptor partial antagonist, memantine, in H4-APP cells and brain tissue of naive mice. EDTA (10 mM), BAPTA (10 microM), and RNAi silencing of IP(3) receptor, NMDA receptor, or SERCA1 attenuated caspase-3 activation. Memantine (4 microM) inhibited isoflurane-induced elevations in cytosolic calcium levels and attenuated isoflurane-induced caspase-3 activation, apoptosis, and cell viability. Memantine (20 mg/kg, i.p.) reduced isoflurane-induced caspase-3 activation in brain tissue of naive mice. These results suggest that disruption of calcium homeostasis underlies isoflurane-induced caspase activation and apoptosis. We also show for the first time that the NMDA receptor partial antagonist, memantine, can prevent isoflurane-induced caspase-3 activation and apoptosis in vivo and in vitro. These findings, indicating that isoflurane-induced caspase activation and apoptosis are dependent on cytosolic calcium levels, should facilitate the provision of safer anesthesia care, especially for Alzheimer's disease and elderly patients.
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PMID:Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine. 1843 34

The spontaneously hypertensive rats (SHR) were fed with nitric oxide synthase (NOS) blocker 7-nitroindazole (7-NI, 10 mg/kg/day) for 6 weeks and an expression of intracellular calcium channels, SERCA and proapoptotic agents was evaluated in kidney. Treatment of rats with 7-NI resulted in a significant increase in mRNA and protein levels of the IP3 receptors type 1 and type 2, while mRNA levels of the IP3 receptor type 3 remained unchanged. The mRNA of other intracellular calcium channels, ryanodine receptors type 1 and type 2 was also upregulated by 7-NI treatment. Gene expression of the SERCA2a, calcium pump responsible for loading intracellular stores with calcium, revealed increased gene expression due to 7-NI as well. Interestingly, proapoptotic agents caspase 3 and Bax were also upregulated by the 7-NI treatment. These results may indicate that nNOS blocker 7-NI modifies intracellular calcium transport system, which may have impact on altered calcium handling and regulation of various metabolic pathways.
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PMID:Effect of 7-nitroindazole on the expression of intracellular calcium channels in the kidney of spontaneously hypertensive rats. 2003 87