Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 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

Minocycline is a tetracycline derivative with antiapoptotic and anti-inflammatory properties, and the drug has been shown to have beneficial effects in a variety of models of neurological disorders. The potentially neuroprotective role of minocycline was assessed in experimental in vitro and in vivo models of rabies virus infection. In this study, 5 nM minocycline did not improve the viability of embryonic mouse cortical and hippocampal neurons infected in vitro with the attenuated SAD-D29 strain of rabies virus, based on assessments using trypan blue exclusion. Two-day-old ICR mice were inoculated in the right hind limb thigh muscle with SAD-D29, and they received daily subcutaneous injections of either 50 mg/kg minocycline or vehicle (phosphate-buffered saline). Infected minocycline-treated mice experienced an earlier onset of neurologic signs and greater mortality (83% versus 50%) than those receiving vehicle (log rank test, P=0.002 and P=0.003, respectively). Immunohistochemical analysis of rabies virus antigen distribution was performed at early time points and in moribund mice. There were greater numbers of infected neurons in the regional brain areas of minocycline-treated mice than in vehicle-treated mice, which was significant in the CA1 region of the hippocampus. There was less apoptosis (P=0.01) and caspase 3 immunostaining (P=0.0008) in the midbrains of mice treated with minocycline than in mice treated with vehicle, consistent with a neuroprotective role of neuronal apoptosis that may have had a mild effect of inhibiting viral spread. Reduced infiltration of CD3+ T cells was observed in the pons/medulla of moribund mice that received minocycline therapy (P=0.008), suggesting that the anti-inflammatory actions of minocycline may intensify the neurologic disease. These findings indicate that minocycline has important detrimental effects in the therapy of experimental rabies. Empirical therapy with minocycline should therefore be approached with caution in cases of human rabies and possibly other viral encephalitides until more experimental data become available.
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PMID:Therapy with minocycline aggravates experimental rabies in mice. 1740 47

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