title: Impact of Heat Shock Protein A 12B Overexpression on Spinal Astrocyte Survival Against Oxygen-Glucose-Serum Deprivation/Restoration in Primary Cultured Astrocytes.
abstract: Heat shock protein A 12B (HSPA12B) is a newly discovered member of the heat shock protein 70 family. Preclinical evidence indicates that HSPA12B helps protect the brain from ischemic injury, although its specific function remains unclear. The aim of this study is to investigate whether HSPA12B overexpression can protect astrocytes from oxygen-glucose-serum deprivation/restoration (OGD/R) injury. We analyzed the effects of HSPA12B overexpression on spinal cord ischemia-reperfusion injury and spinal astrocyte survival. After ischemia-reperfusion injury, we found that HSPA12B overexpression decreased spinal cord water content and infarct volume. MTT assay showed that HSPA12B overexpression increased astrocyte survival after OGD/R treatment. Flow cytometry results showed a marked inhibition of OGD/R-induced astrocyte apoptosis. Western blot assay showed that HSPA12B overexpression significantly increased regulatory protein B-cell lymphocyte 2 (Bcl-2) levels, whereas it decreased expression of the Bax protein, which forms a heterodimer with Bcl-2. Measurements of the level of activation of caspase-3 by Caspase-Glo®3/7 Assay kit showed that HSPA12B overexpression markedly inhibited caspase-3 activation. Notably, we demonstrated that the effects of HSPA12B on spinal astrocyte survival depended on activation of the PI3K/Akt signal pathway. These findings indicate that HSPA12B protects against spinal cord ischemia-reperfusion injury and may represent a potential treatment target.
authors.affiliation: Postgraduate Department, Third Military Medical University, Chongqing, 400038, China.|Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Yang
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Jing-Ming
authors.initials: JM
authors.lastname: Cheng
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Ke-Xia
authors.initials: KX
authors.lastname: Fan
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Yun-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: En-Yu
authors.initials: EY
authors.lastname: Liu
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China.
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Huang
authors.affiliation: Department of Neurological Surgery, The 306th Hospital of PLA, N0.9 Anxiang Beili, Chaoyang District, Beijing, 100101, China. jianwengubj@163.com.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Gu
authors.affiliation: Department of Neurological Surgery, Chengdu Military General Hospital, No.270 Rongdu Road, Chengdu, Sichuan Province, 610083, China. yongqinkuang@126.com.
authors.forename: Yong-Qin
authors.initials: YQ
authors.lastname: Kuang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; C552943:HSPA12B protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D005947:Glucose; D010100:Oxygen
keywords: Apoptosis; Astrocytes; Heat shock protein A 12B; Spinal cord ischemia-reperfusion injury; Survival