Hypoxic remodelling of Ca2+signalling in SH-SY5Y cells: influence of glutathione.
Prolonged hypoxia alters various cellular processes, including Ca2+ signalling. As these effects can be prevented by antioxidants, we examined the role of glutathione, the major intracellular redox buffer, in modulation of Ca2+ signalling in the human neuroblastoma SH-SY5Y by hypoxia. Rises of [Ca2+]i evoked by bradykinin, and subsequent capacitative Ca2+ entry, were enhanced by prior hypoxia (1% O2, 24 h) without effect on reduced glutathione levels. Glutathione depletion reversed the effects of chronic hypoxia, but did not affect normoxically cultured cells. Elevation of glutathione levels also prevented the effects of hypoxia, but restored such effects in glutathione-depleted cells. Glutathione is therefore required for hypoxia to modify Ca2+ signalling, but its role is more complex than simple buffering of reactive oxygen species.
Hettiarachchi
Nishani T
NT
School of Medicine, University of Leeds, Leeds, UK.
Wilkinson
Jenny A
JA
Boyle
John P
JP
Peers
Chris
C
D001920:Bradykinin / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002330:Carmustine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D009447:Neuroblastoma / Q000378:metabolism
D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D005978:Glutathione; D001920:Bradykinin; D002330:Carmustine