title: Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway.
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.
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China ; Department of Traditional Chinese Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Bingwu
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Hu
authors.affiliation: National Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Tonglin
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Liuwang
authors.initials: L
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency*; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D050886:HSP20 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D000077614:Golgi Matrix Proteins; D050886:HSP20 Heat-Shock Proteins; D033921:Vesicular Transport Proteins; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C091580:vesicular transport factor p115; D053148:Caspase 3; D005947:Glucose; D010100:Oxygen