Roscovitine inhibits ERK1/2 activation induced by angiotensin II in vascular smooth muscle cells

Abstract

Roscovitine is a potent CDK inhibitor often used as a biological tool in cell-cycle studies, but its working mechanism and real targets in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we observed that ERK1/2 phosphorylation induced by Ang II was abrogated by pretreating VSMCs with roscovitine for 15 h. Pretreating VSMCs with roscovitine also inhibited Ang II-induced c-Jun expression and phosphorylation. We further demonstrated that roscovitine could suppress the DNA binding activity of c-Jun and activation of angiotensinogen promoter by Ang II. These results suggest that roscovitine represses Ang II-induced angiotensinogen expression by inhibiting activation of ERK1/2 and c-Jun.

A Novel Roscovitine Derivative Potently Induces G1-Phase Arrest in Platelet-Derived Growth Factor-BB-Activated Vascular Smooth Muscle Cells

“…4). Although previous reports implicated an interference of ROSC with MAPK activation (Bach et al, 2005;Li et al, 2008), our results were further corroborated even when using higher concentrations of both compounds (10 M LGR1406 and 25 M ROSC) and prolonged time of preincubation (15 h) (data not shown).…”

“…Although ROSC has been studied extensively in different cell types for its antiproliferative influence, there are only two publications addressing its effect on VSMC growth using angiotensin II (Ang II) and serum as stimuli, respectively (O'Sullivan et al, 2003;Li et al, 2008). Neither of these studies provides data regarding ROSC and PDGF signaling.…”

“…The study by Li et al (2008) using Ang-II-activated VSMCs identifies ROSC as an inhibitor of ERK phosphorylation and activity, a mechanism that could be excluded in our setting. Reasons for this discrepancy could be next to the differing stimulus (Ang II versus PDGF), the pretreatment of cells for 15 h with ROSC before Ang II stimulation by Li et al, which may lead to secondary indirect effects due to changes in protein expression.…”

The cyclin‐dependent kinase inhibitor R‐roscovitine down‐regulates Mcl‐1 to override pro‐inflammatory signalling and drive neutrophil apoptosis

“…This contrasts with work on vascular smooth muscle cells where R-roscovitine inhibited ERK activation by angiotensin II [39]. It seems likely that the early, dramatic effects of R-roscovitine on neutrophil survival are unlikely to be due to this sub-optimal inhibition of ERK phosphorylation.…”

Krüppel-like factor 4 interacts with p300 to activate mitofusin 2 gene expression induced by all-trans retinoic acid in VSMCs

“…ChIP assays were performed as described previously [21,22] . In brief, VSMCs at 80% confluence were crosslinked with 1% formaldehyde for 10 min, lysed and sonicated 5-10 times each for 10 s at 4 °C to reduce the average DNA length to 0.4-0.5 kb.…”