D. O. Minchenko^1,2,3, O. V. Hubenya¹, B. M. Terletsky¹,
M. Moenner³, O. H. Minchenko^1,3

¹Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com;
²National O. O. Bohomoletz Medical University, Kyiv, Ukraine;
³INSERM U920 Molecular Mechanisms of Angiogenesis Laboratory,
University Bordeaux 1, Talence, France

Ischemia has been shown to induce a set of complex intracellular signaling events known as the unfolded protein response, which is mediated by endoplasmic reticulum–nuclei-1 sensing enzyme. We have studied the expression of several cyclin and cyclin-dependent kinase genes which participate in the control of cell cycle and proliferation under ischemic conditions (glucose or glutamine deprivation) in endoplasmic reticulum–nuc­lei 1-deficient glioma cells. It was shown that blockade of endoplasmic reticulum–nuclei signaling enzyme-1, the key endoplasmic reticulum stress sensor, leads to an increase of the expression levels of cyclin-dependent kinase-2 and cyclin A2, D3, E2 and G2 genes but suppresses cyclin D1. Moreover, the expression level of cyclin-dependent kinase-2 as well as cyclin A2, D3 and E2 mRNAs is significantly decreased under glucose or glutamine deprivation conditions both in control and endoplasmic reticulum–nuclei-1-deficient glioma cells. However, cyclin-dependent kinase-4 and -5 mRNA expressions is increased, but in glucose deprivation conditions only.  Results of this study have shown that the expression of most tested genes of encoded cyclins and cyclin-dependent kinases is dependent on endoplasmic reticulum–nuclei-1 signaling enzyme function both in normal and glutamine and glucose deprivation conditions and possibly participates in cell adaptive response to endoplasmic reticulum stress associated with ischemia.

Keywords: cyclin A2_D1_D3_E2 and G2, cyclin-dependent kinase-2_-4 and -5, endoplasmic reticulum–nuclei-1, glioma cells, glucose and glutamine deprivation, mRNA expression