Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Invasion of the cultured epithelial cell lines HeLa, Henle-407, and Caco-2 (polarized and nonpolarized) by Salmonella typhi and Salmonella typhimurium were compared using conventional gentamicin invasion assays. Additionally, the mechanisms of invasion and intracellular trafficking by S. typhi and S. typhimurium were compared in HeLa cells using indirect immunofluorescence microscopy. S. typhi strain Ty2 was invasive in all human cell lines tested, including apical uptake into polarized Caco-2 cell monolayers. This strain also replicated at levels similar to S. typhimurium strain SL1344 inside HeLa and Henle-407 cells. Indirect immunofluorescence microscopy confirmed that S. typhi, like S. typhimurium, induced membrane ruffles and cytoskeletal rearrangements upon contact with HeLa cell surfaces. Ruffling induced by S. typhi and S. typhimurium was accompanied by macropinocytosis of the fluid phase endocytic marker fluorescein-dextran-sulphate and by aggregation of cell surface class I MHC heavy chain. Intracellular lysosomal trafficking of S. typhi and S. typhimurium in HeLa cells was also studied. The lysosomal membrane glycoprotein marker h-lamp-2 colocalized with S. typhi-containing vacuoles, as previously shown for S. typhimurium. The soluble lysosomal enzyme marker cathepsin D also was found within S. typhi-containing vacuoles to the same extent as previously published for S. typhimurium. The results from this study suggest that S. typhi and S. typhimurium use similar mechanisms for invasion and intracellular trafficking in cultured human epithelial cells.
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PMID:Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. 775 82

We tested the hypothesis that ischemic postconditioning (IPost) induces autophagy and the activation of autophagy contributes to the cardioprotective effects against ischemia/reperfusion injury in rat hearts. Rats were subjected to IPost established by 3 cycles of 10-second reperfusion followed by 10-second ischemia at the end of 30-minute ischemia. The activation of autophagy was assessed by the morphological and biochemical examinations after 120-minute reperfusion in ventricular tissue. To investigate the contribution of autophagy to IPost, the rats were pretreated with the autophagy inhibitor 3-methyl-adenine (3-MA). We found that IPost increased the formation of autophagic vacuoles, the autophagic-related protein levels of LC3-II, Beclin1, lysosome-associated membrane protein 2, and cathepsin D, and the mRNA level of LC3 and Beclin1 in the risk zone of the postconditioned hearts. Furthermore, 3-MA treatment significantly reversed the reduction effect of IPost on infarct volume, and in the meantime, inhibited the induction of LC3 and Beclin1. In addition, 3-MA treatment inhibited the antiapoptotic-related protein levels of Bcl-2 and increased the apoptotic-related protein levels of Bad. Taken together, these results indicate that the protective effects of IPost are associated with the activation of autophagy in rat hearts.
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PMID:Activation of autophagy in ischemic postconditioning contributes to cardioprotective effects against ischemia/reperfusion injury in rat hearts. 2336 9

Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule-associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2-acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis.
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PMID:Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis. 2615 32