Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poliovirus and some other picornaviruses trigger relocation of certain nuclear proteins into the cytoplasm. Here, by using a protein changing its fluorescence color with time and containing a nuclear localization signal (NLS), we demonstrate that the poliovirus-triggered relocation is largely due to the exit of presynthesized nuclear protein into the cytoplasm. The leakiness of the nuclear envelope was also documented by the inability of nuclei from digitonin-permeabilized, virus-infected (but not mock-infected) cells to retain an NLS-containing derivative of green fluorescent protein (GFP). The cytoplasm-to-nucleus traffic was also facilitated during infection, as evidenced by experiments with GAPDH (glyceraldehyde-3-phosphate dehydrogenase), cyclin B1, and an NLS-lacking derivative of GFP, which are predominantly cytoplasmic in uninfected cells. Electron microscopy demonstrated that a bar-like barrier structure in the channel of the nuclear pores, seen in uninfected cells, was missing in the infected cells, giving the impression of fully open pores. Transient expression of poliovirus 2A protease also resulted in relocation of the nuclear proteins. Lysates from poliovirus-infected or 2A-expressing cells induced efflux of 3xEGFP-NLS from the nuclei of permeabilized uninfected cells. This activity was inhibited by the elastase inhibitors elastatinal and N-(methoxysuccinyl)-L-alanyl-L-alanyl-L-prolyl-L-valine chloromethylketone (drugs known also to be inhibitors of poliovirus protease 2A), a caspase inhibitor zVAD(OMe), fmk, and some other protease inhibitors. These data suggest that 2A elicited nuclear efflux, possibly in cooperation with a zVAD(OMe).fmk-sensitive protease. However, poliovirus infection facilitated nuclear protein efflux also in cells deficient in caspase-3 and caspase-9, suggesting that the efflux may occur without the involvement of these enzymes. The biological relevance of nucleocytoplasmic traffic alterations in infected cells is discussed.
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PMID:Bidirectional increase in permeability of nuclear envelope upon poliovirus infection and accompanying alterations of nuclear pores. 1533 49

In mammalian cells, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) has recently been shown to be implicated in numerous apoptotic paradigms, especially in neuronal apoptosis, and has been demonstrated to play a vital role in some neurodegenerative disorders. However, this phenomenon has not been reported in protists. In the present study, we report for the first time that such a mechanism is involved in diclazuril-induced apoptosis in Eimeria tenella (E. tenella). We found that upon treatment of parasites with diclazuril, the expression levels of GAPDH transcript and protein were significantly increased in second-generation merozoites. Then, we examined the subcellular localization of GAPDH by fluorescence microscopy and Western blot analysis. The results show that a considerable amount of GAPDH protein appeared in the nucleus within diclazuril-treated second-generation merozoites; in contrast, the control group had very low levels of GAPDH in the nucleus. The glycolytic activity of GAPDH was kinetically analyzed in different subcellular fractions. A substantial decrease (48.5%) in glycolytic activity of GAPDH in the nucleus was displayed. Moreover, the activities of caspases-3, -9, and -8 were measured in cell extracts using specific caspase substrates. The data show significant increases in caspase-3 and caspase-9 activities in the diclazuril-treated group.
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PMID:Nuclear translocation and accumulation of glyceraldehyde-3-phosphate dehydrogenase involved in diclazuril-induced apoptosis in Eimeria tenella (E. tenella). 2365 Dec 14

Emodin is a natural anthraquinone derivative that occurs in many Chinese medicinal herbs. It might induce liver damage, but the mechanism is not clear. In this research, seven groups of Sprague-Dawley (SD) rats with three doses of emodin were used. The liver injury was examined by analyzing biochemical indexes and histopathology. Altered proteins between the control group (CG) and the liver injury group were determined by proteomic technology. The results showed that emodin causes liver injury in a time- and dose-dependent manner. In the high-dosage 1-week group (HG1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was downregulated, and the activity of malate dehydrogenase (MDH) was inhibited by emodin. These might cause the inhibition of FADH or NADH/NADPH transport from the cytoplasm to mitochondria. The WB results showed that the inhibition of FADH/NADPH transport induced a high activity of caspase-9 and caspase-3, and the expressions of cytochrome c (Cyt C), caspase-9 and caspase-3 were high in HG1, which might lead to mitochondrial apoptosis pathway activation. In addition, whatever the HG1 or low-dose group (LG), the effects of emodin on mitochondria were observed. Overall, for the first time, we showed that emodin inhibited proton transport and induced the activation of the mitochondrial apoptosis pathway, which might be the reason for liver injury.
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PMID:Emodin induces liver injury by inhibiting the key enzymes of FADH/NADPH transport in rat liver. 3031 Jun 65