Hsp20 protects neuroblastoma cells from ischemia/reperfusion injury by inhibition of apoptosis via a mechanism that involves the mitochondrial pathways.

Abstract

Hsp20 is chaperone protein that is highly and constitutively expressed in the brain, cardiac tissue and many other organs. Recently, it is well established that Hsp20 can enhance cardiac function and render cardioprotection. However, the potential benefits of Hsp20 and its phosphorylation form action on ischemic stroke and its underlying mechanism(s) are largely unknown.To investigate whether Hsp20 exerts protective effects in vitro ischemia/reperfusion (I/R) injury, mouse neuroblastoma cells were subjected to oxygen-glucose deprivation (OGD) and reoxygenation. Expression mRNA and protein levels of Hsp20 were strongly downregulated in mouse N2A cells at the 0-hour and 6-hour recovery time points following 4 hours of OGD, and returned to basal level 12 and 24 hours after OGD treatment. The ratio of phosphorylated to total Hsp20 protein was not significantly affected by OGD treatment at the 0-hour and 6-hour recovery time points following 4 hours of OGD. However, markedly higher serine phosphorylation of Hsp20 was observed 12 and 24 hours after OGD treatment. Furthermore, overexpression of Hsp20 reduced OGD-induced apoptosis by reducing the release of cytochrome c from mitochondria to cytosol. However, blockade of Hsp20 phosphorylation at Ser16 abrogated this anti-apoptotic effect.Our data demonstrate that increased Hsp20 expression in mouse N2A neuroblastoma cells protects against I/R injury, resulting in reduced apoptosis, which is by reducing the release of cytochrome c from mitochondria to cytosol. Phosphorylation of Ser16 plays an important role in its protective effect. Thus, Hsp20 may constitute a new therapeutic target for cerebral ischemic diseases.

• Authors: Liuwang Zeng, Jieqiong Tan, Zhiping Hu, Wei Lu, Binbin Yang
• Journal: Current neurovascular research (Curr Neurovasc Res) Vol. 7 Issue 4 Pg. 281-7 (Nov 2010) ISSN: 1875-5739 [Electronic] United Arab Emirates
• PMID: 20854253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HSP20 Heat-Shock Proteins
• RNA, Messenger
• enhanced green fluorescent protein
• Green Fluorescent Proteins
• Cytochromes c
• Glucose

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Gene Expression Regulation, Neoplastic (physiology)
• Glucose (deficiency)
• Green Fluorescent Proteins (genetics)
• HSP20 Heat-Shock Proteins (genetics, metabolism)
• Hypoxia (metabolism)
• Mice
• Mitochondria (metabolism)
• Mutation
• Neuroblastoma (pathology, ultrastructure)
• Phosphorylation (physiology)
• RNA, Messenger (metabolism)
• Time Factors