The Involvement of Protein Kinase C-βII in Glucose-Induced Rat Vascular Smooth Muscle Cell Proliferation

Publisher Website
Google Scholar
Abstract
The protein kinase C (PKC)-βII modulates glucose-induced cell proliferation in A10 cells, a clonal cell line of vascular smooth muscle cells (VSMC) from rat aorta, which were studied by overexpressing PKC-βII and using a PKC-βII specific inhibitor (CG53353). PKC-βII overexpression was verified by the fourfold increase of PKC enzyme activity and PKC-βII immunoreactivity. Overexpression of PKC-βII attenuated A10 cell proliferation and DNA synthesis through the suppression of cell cycle progression inhibiting the entry of cells into the S phase. High glucose (25 mM) increased and accelerated cell proliferation, DNA synthesis, and the percentage of cells entering the S phase in A10. High glucose down-regulated PKC-βII in A10 cells during the first cell cycle after cell synchronization. CG53353 inhibited glucose-induced cell proliferation and DNA synthesis specifically. These results suggest that PKC-βII has inhibitory functions as a cell cycle checkpoint mediator during the late G1 phase and may regulate the S phase entry. High glucose down-regulates endogenous PKC-βII, which alters its normal role in cell cycle progression, and results in stimulation of VSMC proliferation through acceleration of the cell cycle. CG53353 might release cells from the PKC-βII regulated checkpoint of the cell cycle.