Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven-day-old ICR mice were infected by intracerebral inoculation with recombinant rabies virus vaccine strain SAD-L16. Infected mice developed severe and fatal encephalitis with rabies virus-infected neurons in widespread regions of the brain. There was extensive neuronal death with predominant features of apoptosis, as assessed by light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, and immunohistochemical staining for activated caspase-3. Although SAD-L16 is a neuroattenuated rabies virus, it is fully capable of spreading efficiently and inducing widespread neuronal apoptosis in the immature mouse brain.
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PMID:Recombinant rabies virus vaccine strain SAD-l16 inoculated intracerebrally in young mice produces a severe encephalitis with extensive neuronal apoptosis. 1597 73

The accumulation of unfolded protein in lumen of the endoplasmic reticulum (ER) triggers a cell stress response called ER stress, which induces the transcriptional up-regulation of a number of proteins, including molecular chaperones and folding enzymes, the global inhibition of protein synthesis, and the activation of apoptotic pathways. The molecular mechanism underlying the apoptotic response has remained largely elusive. AMP activated protein kinase (AMPK) has been implicated in ER stress-induced apoptosis through its role in attenuating ER stress. BRSK2 (brain selective kinase 2, also known as SAD-A) is a serine/threonine kinase of the AMPK family. Here, we demonstrate that the BRSK2 protein levels are significantly down-regulated in response to ER stress in PANC-1 and HeLa cells. Furthermore, we also observed that ER stress induces endogenous BRSK2 to localize to the ER. Importantly, knockdown of endogenous BRSK2 expression enhances ER stress-mediated apoptosis in cells while over express BRSK2 in wild type or kinase-dead type both reduce the apoptosis. BRSK2 knockdown increases the transcription of CHOP and the levels of cleaved caspase-3 in cells in response to ER stress while over expression of BRSK2 decrease CHOP mRNA and levels of cleaved caspase-3. Taken together, our findings demonstrate ER stress may reduce BRSK2 protein and change BRSK2 subcellular localization, which in turn alleviate ER stress-induced apoptosis.
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PMID:BRSK2 is regulated by ER stress in protein level and involved in ER stress-induced apoptosis. 2271 62

4,4'-bond secalonic acid D (4,4'-SAD) is a known compound isolated from the marine-derived fungus Penicillium oxalicum. No study about the antitumor effect of this compound has been reported, except for a few focusing on its bactericidal properties. Herein, we performed an in vitro biology test and found that 4,4'-SAD stimulated the apoptosis of tumor cells in the human hepatocellular carcinoma cell lines PLC/PRF/5 and HuH-7 by activating caspase-3, caspase-8, caspase-9, PARP, p53, and cyclin B1, as well as by regulating the Bax/Bcl-2 ratio. In vivo studies showed that 4,4'-SAD had antitumor efficacy in H22 cell xenograft model. Immunohistochemical analysis revealed that 4,4'-SAD could regulate Bax expression, which is a biomarker of tumor growth. In summary, 4,4'-SAD significantly inhibited tumor growth both in vivo and in vitro.
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PMID:Isolation of 4,4'-bond secalonic acid D from the marine-derived fungus Penicillium oxalicum with inhibitory property against hepatocellular carcinoma. 3025 23