低氧低糖剥夺通过缺氧诱导因子-1途径对脑-胰腺相关蛋白表达的抑制作用。

Inhibitive effects of low oxygen and glucose deprivation on brain-pancreas relative protein expression via hypoxia- inducible factor-1 pathways.

作者信息

Lin Yanhua, Liu Aihua, Lu Ning, Li Yuhua, Song Qianliu, Yu Heming, Li Xuejun

机构信息

Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing, PR China.

出版信息

Cell Physiol Biochem. 2008;22(1-4):353-62. doi: 10.1159/000149814. Epub 2008 Jul 25.

DOI:10.1159/000149814

PMID:18769063

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 Ca(2+) concentration (Ca(2+)), 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+), 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.

CONCLUSION

All together, our observations suggest that calcium, p38 MAPK activation and HIF-1alpha are necessary for LOGD-reduced BPRP expression in PC12 cells.

摘要

背景

脑胰腺相关蛋白（BPRP）是我们实验室发现的一种新蛋白，在缺血大鼠脑中表达降低。然而，缺血期间调节BPRP表达的机制仍需进一步研究。

方法

在本研究中，我们用低氧低糖剥夺（LOGD，一种体外缺血模型）培养基培养PC12细胞，然后检测LOGD条件下BPRP表达的信号转导通路。

结果

发现LOGD显著降低BPRP表达，但增加细胞内钙离子浓度（[Ca(2+)]i）、p38丝裂原活化蛋白激酶（MAPK）磷酸化水平以及缺氧诱导因子1α亚基（HIF-1α）的表达。然而，BAPTA-AM（一种细胞内钙螯合剂）、SB 203580（一种p38抑制剂）和HIF-1α反义核酸分别显著抑制[Ca(2+)]i、p38 MAPK磷酸化水平和HIF-1α表达。我们的结果还表明，BAPTA-AM可降低p38 MAPK磷酸化水平，SB203580和BAPTA-AM可抑制HIF-1α表达，这表明在LOGD过程中，钙、p38 MAPK和HIF-1α处于同一信号转导通路。值得注意的是，SB203580、BAPTA-AM和HIF-1α反义核酸可恢复LOGD导致的BPRP表达降低。