Hypoxia modulates gene expression of IP3 receptors in rodent cerebellum.
Hypoxic brain cell injury is a complex process that results from a series of intracellular events. In this work, we tested whether severe hypoxia for 6 h can affect gene expression and protein levels of intracellular calcium channels, ryanodine receptors, and inositol 1,4,5-trisphosphate receptors in mouse cerebellum. In addition, we tested the effect of hypoxia on cerebellar granular cells of rats. We have found that gene expression of types 1 and 2 IP(3) receptors is significantly increased after the exposure of mice to hypoxic stimulus for 6 h and also in rat cerebellar granular cells. Increased gene expression of IP(3) receptors was reflected in increased protein levels of these channels as well. In this process, reactive oxygen species are most probably involved, as antioxidant quercetin abolished hypoxia-induced increase in both types 1 and 2 IP3 receptor. Ryanodine receptors of types 1 and 2 and sarco(endo)plasmic reticulum Ca(2+)-ATPase were not affected by hypoxia on the level of messenger RNA. To test physiological consequences, we measured levels of intracellular calcium. We observed significantly elevated calcium level in hypoxic compared to normoxic cells. Deeper understanding of mechanisms, through which hypoxia regulates intracellular calcium, could point towards the development of new therapeutic approaches to reduce or suppress the pathological effects of cellular hypoxia, such as those seen in stroke or ischemia.
Jurkovicova
D
D
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska 5, 833 34, Bratislava, Slovakia.
Kopacek
J
J
Stefanik
P
P
Kubovcakova
L
L
Zahradnikova
A
A
Zahradnikova
A
A
Pastorekova
S
S
Krizanova
O
O
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D002534:Hypoxia, Brain / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D017931:DNA Primers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger