Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway.

Bingwu Zhong,Zhiping Hu,Liuwang Zeng,Qiang Lei,Chunli Chen,Jieqiong Tan,Tonglin Lu

doi:10.1155/2015/606934

Abstract

Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA) is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders.

Highlights

The Golgi apparatus (GA) is a pivotal organelle in cell metabolism and participates in many vital processes, such as oxidative stress, signal transduction, and cell apoptosis
To explore whether Golgi fragmentation occurs in N2a cells without transfection upon oxygen-glucose deprivation/reperfusion (OGDR) insult, we used immunofluorescent staining to evaluate its temporal profiles (Figure 1)
Does a reduced cerebral blood supply lead to substantial brain tissue damage, and reperfusion contributes to the poor outcomes after ischemic stroke

Summary

Introduction

The Golgi apparatus (GA) is a pivotal organelle in cell metabolism and participates in many vital processes, such as oxidative stress, signal transduction, and cell apoptosis. P115 is a 961 kDa Golgi-associated peripheral membrane protein. It forms homodimers and mediates several docking steps and vesicle transport. Small heat shock proteins are molecular chaperones and some of them have been suggested to be protective in neurological disorders induced by protein misfolding [9, 10]. Hsp is one of the small heat shock proteins. It plays a vital role in modulating many physiological conditions, as well as in protecting against an amount of pathological processes [11]. We previously have demonstrated that Hsp attenuates mitochondrial fragmentation and exerts protection against oxygen-glucose deprivation/reperfusion (OGDR)

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