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

Summary: Protein kinase C beta 2 has something to do with cells entering S-phase, at least for vascular smooth muscle cells from rats' aortas.

Interestingness: 1


Paper by Mayumi Yamamoto, Niketa A Patel and Denise R Cooper in the Journal of Anti-Aging Medicine, Volume 1, Issue 3, Fall 1998.

(((All that growth hormone has destroyed my wishes to summarise everything. I'm going to stick to the ones I find interesting, and only write brief highlights of the rest, like in the case of this one)))

(((The abstract says about everything I would write about this paper and is way clearer because I don't understand the result presented)))

Protein kinase C - beta II (PKC-B2) overexpression slowed down replication of vascular smooth muscle cells (VSMC) extracted from rats' aortas (((VSMC proliferation is likely a bad thing for atherosclerosis))). High glucose levels downregulate PKC-B2 in the short term (((but raise it long term))) and speed up VSMC replication. CG53353 is a PKC-B2 inhibitor (((but adding it doesn't seem to speed up replication of VSMC))). It makes the cells ignore the glucose levels with regards to replication speed. Glucose usually speeds up the rate at which cells enter S-phase (((DNA-replication step of cell replication))). This is consistent with PKC-B2 being a controller of when cells go into S-phase (((but the picture seems confusing to me. Why doesn't adding CG53353 raise VSMC replication? It does on cells that overexpress PKC-B2, but not in standard ones. Why?)))


Abstract follows:

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.