ABSTRACT
Monocyte chemoattractant protein-1 (MCP-1) has been reported to induce the expression of monocyte chemotactic protein-induced protein 1 (MCPIP1), which undergoes ubiquitination degradation. Therefore, we predict that in vascular smooth muscle (VSMCs), MCPIP1 may be induced by MCP-1 and undergo degradation, which can be inhibited by the proteasome inhibitor, MG132. Our results showed that treatment of human VSMCs with MCP-1 did not increase the expression of MCPIP1. Treatment with MG132, however, elevated MCPIP1 protein levels through stimulation of the gene transcription, but not through increasing protein stability. MCPIP1 expression induced by MG132 was inhibited by α-amanitin inhibition of gene transcription or cycloheximide inhibition of protein synthesis. Our further studies showed that MCPIP1 expression induced by MG132 was inhibited by the inhibitors of AKT and p38 kinase, suggesting a role of the AKT-p38 pathway in MG132 effects. We also found that treatment with MG132 induces apoptosis, but overexpression of MCPIP1 inhibited bromodeoxyuridine (BrdU) incorporation of human VSMCs without induction of significant apoptosis. In summary, MCPIP1 expression is induced by MG132 likely through activation of the AKT-p38 pathway. MCPIP1 inhibits SMC proliferation without induction of apoptosis. J. Cell. Physiol. 232: 122-128, 2017. © 2016 Wiley Periodicals, Inc.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Chemokine CCL2/metabolism , Leupeptins/pharmacology , Muscle, Smooth, Vascular/drug effects , Proteasome Inhibitors/pharmacology , Cells, Cultured , Humans , Muscle, Smooth, Vascular/cytology , Transcription Factors/metabolismABSTRACT
The present study reports the structural and functional changes of myocardial muscarinic receptor during early and late septic shock, Septic shock was induced by caecum ligation and puncture (CLP). The results showed that the number of M receptor on sarcolemma (SL) increased and that on the light vesicle (LV) decreased during early septic shock. The (3)H-QNB binding of M receptor on SL increased by 33.37%. By contrast during late septic shock, the number of M receptor on LV increased and that on SL decreased. The (3)H-QNB binding of LV M receptor was increased by 29.26%. At the same time phosphorylation of the M receptor was decreased during early septic shock and increased during late septic shock. These results suggest that the changes of M receptors may be related to the myocardial dysfunction during septic shock.
