Search

Inflammatory cytokines are able to induce vascular smooth muscle cells (VSMCs) to undergo apoptosis, causing atherosclerotic plaque rupture. Changes in the e×pression levels of conne×ins (C×s) have been demonstrated in VSMCs to be involved in the pathogenesis of atherosclerotic progression. The present study e×amined the effect of tumor necrosis factor-ɑ (TNF-ɑ) on C×43 e×pression levels and apoptosis in human VSMCs. Overe×pression of C×43 plasmids notably stimulated VSMC proliferation. TNF-ɑ directly inhibited C×43 e×pression levels in a dose- and time-dependent manner in VSMCs, however this was blocked by c-Jun N-terminal kinase inhibitor. TNF-ɑ also increased caspase-3 activity and apoptosis of VSMCs through the inhibition of C×43. These data suggested that TNF-ɑ induced the apoptosis of VMSCs and prompted the destabilization of atherosclerotic plaques by downregulating C×43. [ABSTRACT FROM AUTHOR]

Background/Aims: Glutamine showed cytoprotective activ-ity in vitro on anoxia-reoxygenation injury via induction of heme oxygenase-1 (HO-1). We thus investigated its in vivo tissue-protective effect in a rat liver ischemia-reperfusion (l/R) model. Methods: Before the l/R procedure, animals were treated with glutamine. Liver injury was evaluated by serum liver enzymes, histological examination and apopto-sis detection bytransferase-mediated uridine nick end label-ing staining. Meanwhile, expression and activities of HO-1 were measured by Western blot and a biochemical method. Liver blood flow was measured by using a laser Doppler flowmeter, and oxidative injury was Investigated by the thio-barblturic acid-reactive substance (TBARS) assay. The inflam-matory cytokine monocyte chemotactic protein (MCP)-1 was quantified by ELISA. Results: l/R caused a large increase in levels of liver enzymes, remarkably Inducing the necrosis and apoptosis of liver tissue, which was markedly Inhibited by glutamine, during which HO-1 was upregulated signifi-cantly, and the HO-1 inhibitor zinc protoporphyrin nullified the effect of glutamine. Liver blood flow was greatly reduced after l/R; however, it was significantly improved by gluta-mine. Lipid peroxidation (TBARS) in liver tissue was largely induced which was significantly lowered by glutamine. Sim-ilar results were also observed for the production of MCP-1. Conclusion: Glutamine protected tissue against oxidative injury during rat hepatic l/R, by induction of HO-1 to fulfill antioxidative and antiapoptotic effects. [ABSTRACT FROM AUTHOR]