Inhibitive effects of low oxygen and glucose deprivation on brain-pancreas relative protein expression via hypoxia- inducible factor-1 pathways.
BACKGROUND
Brain-Pancreas Relative Protein (BPRP), a novel protein discovered in our lab, was decreased in ischemic rat brain. However, the mechanisms regulating BPRP expression during ischemia need further investigation.


METHODS
In the present study we cultured PC12 cells with low oxygen and glucose deprivation (LOGD, a model of ischemia in vitro) media, then examined the signal transduction pathways of BPRP expression under LOGD.


RESULTS
It was found that LOGD significantly decreased BPRP expression, but increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), p38 mitogen-activated protein kinases (MAPK) phosphorylation and hypoxia inducible factor 1 alpha subunit (HIF-1alpha) expression. However, BAPTA-AM (an intracellular calcium chelator), SB 203580 (an inhibitor of p38) and HIF-1alpha antisense significantly inhibited the [Ca(2+)](i), p38 MAPK phosphorylation and HIF-1alpha expression respectively. Our results also showed that p38 MAPK phosphorylation was reduced by BAPTA-AM, and HIF-1alpha expression was inhibited by SB203580 and BAPTA-AM, suggesting that calcium, p38 MAPK and HIF-1alpha are in the same signal transduction pathways during LOGD. Noticeably, reduced BPRP expression by LOGD can be recovered by SB203580, BAPTA-AM and HIF-1alpha antisense.


CONCLUSIONS
All together, our observations suggest that calcium, p38 MAPK activation and HIF-1alpha are necessary for LOGD-reduced BPRP expression in PC12 cells.
Lin
Yanhua
Y
Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing, PR China.
Liu
Aihua
A
Lu
Ning
N
Li
Yuhua
Y
Song
Qianliu
Q
Yu
Heming
H
Li
Xuejun
X