Original Paper

Inhibitive Effects of Low Oxygen and Glucose Deprivation on Brain-Pancreas Relative Protein Expression via Hypoxia- Inducible Factor-1 Pathways
Yanhua Lin^a, Aihua Liu^b, Ning Lu^a, Yuhua Li^a, Qianliu Song^a, Yu Yu^c, Xuejun Li<sup>a

a</sup>Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing,
^b School of Pharmaceutical Science, Peking University, Beijing,
^cNational Research Institute for Family Planning, Beijing

Address of Corresponding Author

Cell Physiol Biochem 2008;22:353-362 (DOI: 10.1159/000149814)

  Key Words

• Brain-Pancreas Relative Protein
• Hypoxia-inducible factor-1
• Low oxygen and glucose deprivation
• [Ca²⁺]_i
• p38 MAPK

  Abstract

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 Ca²⁺ concentration ([Ca²⁺]_i), p38 mitogen-activated protein kinases (MAPK) phosphorylation and hypoxia inducible factor 1 subunit (HIF-1) expression. However, BAPTA-AM (an intracellular calcium chelator), SB 203580 (an inhibitor of p38) and HIF-1 antisense significantly inhibited the [Ca²⁺]_i, p38 MAPK phosphorylation and HIF-1 expression respectively. Our results also showed that p38 MAPK phosphorylation was reduced by BAPTA-AM, and HIF-1 expression was inhibited by SB203580 and BAPTA-AM, suggesting that calcium, p38 MAPK and HIF-1 are in the same signal transduction pathways during LOGD. Noticeably, reduced BPRP expression by LOGD can be recovered by SB203580, BAPTA-AM and HIF-1 antisense. Conclusion: All together, our observations suggest that calcium, p38 MAPK activation and HIF-1 are necessary for LOGD-reduced BPRP expression in PC12 cells.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Prof. Xuejun Li
Department of Pharmacology, School of Basic Medical Sciences
Peking University, Beijing 100083, P.R (China)
Tel. +86-10-82802863, Fax: +86-10-62179119
E-Mail xjli@bjmu.edu.cn

  Article Information

Accepted: March 17, 2008
Published online: July 25, 2008
Number of Print Pages : 10