Growth factors upregulate astrocyte [Ca2+]i oscillation by increasing SERCA2b expression.
Previously, we reported upregulation of astrocyte [Ca(2+)](i) oscillation by growth factors (i.e., conversion of glutamate-induced sustained [Ca(2+)](i) increase in astrocytes cultured in a defined medium to [Ca(2+)](i) oscillation by EGF and bFGF treatment over 48 h) (Morita et al., (2003) J Neurosci 23:10944-10952). As our previous study also showed that these growth factors increase intracellular Ca(2+) stores, this study was performed to investigate the mechanism underlying loading of intracellular Ca(2+) stores in astrocytes, especially sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA), as a candidate mechanism by which growth factors upregulate [Ca(2+)](i) oscillation. The results indicated that the growth factors upregulated a SERCA inhibitor-sensitive component of [Ca(2+)](i) clearance, and increased expression of the SERCA subtype, SERCA2b. Furthermore, treating the growth factor-treated astrocytes with a low concentration of SERCA inhibitor to partially inhibit SERCA reduced the level of intracellular Ca(2+) storage and reversed glutamate-induced [Ca(2+)](i) oscillations to sustained [Ca(2+)](i) increases. Thus, the upregulation of [Ca(2+)](i) oscillations was attributed to the upregulation of SERCA activities. These results indicated that these growth factors regulate the pattern of glutamate-induced astrocyte [Ca(2+)](i) increases via SERCA2b expression.
Morita
Mitsuhiro
M
Department of Neurosurgery, University of New Mexico, Albuquerque, New Mexico, USA. mmorita@boar.kobe-u.ac.jp.
Kudo
Yoshihisa
Y
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse