Pengjiu Feng1, Aimin Zhang2, Ming Su3, Hai Cai3, Xiaogang Wang3, Yan Zhang4. 1. Department of Anesthesiology, the Third Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Liuzhou, Guangxi 545001, PR China. Electronic address: fengpengjiu@163.com. 2. Department of Pain, the Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, PR China. 3. Department of Anesthesiology, the Third Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Liuzhou, Guangxi 545001, PR China. 4. Department of Neurology, the Third Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Liuzhou, Guangxi 545001, PR China.
Abstract
OBJECTIVE: There is an increasing interest concerning the contribution of astrocytes to the intrinsic bioremediation of ischemic brain injury. The aim of this work was to disclose the effects and mechanism of dexmedetomidine (DEX) on the apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. METHODS: Primary cultured astrocytes separated from Sprague-Dawley (SD) rats were subjected to OGD treatment. Astrocytes were transfected with si-JMJD3 or pcDNA3.1-JMJD3 and then treated with DEX or JAK/STAT inhibitor (WP1066) before cell apoptosis was detected by TUNEL apoptosis kit. Western blot was applied to assess the level of apoptosis-related proteins Caspase-3, Bax and Bcl-2. Astrocyte cell viability was assessed by measuring the lactate dehydrogenase (LDH) level using a LDH assay kit. RESULTS: Astrocytes received OGD treatment had increased LDH and elevated apoptotic rate (P < 0.05). DEX could suppress OGD induced cytotoxic effect on astrocytes, as evidenced by decreased LDH release and suppressed cell apoptosis rate (P < 0.05). Meanwhile, DEX and WP1066 treatment were also found to inhibit the phosphorylation level of STAT1 and STAT3 (P < 0.05), indicating the DEX could suppress the activation of JAK/STAT signal pathway. JMJD3 overexpression in astrocytes could suppress the anti-apoptotic function of WP1066 in OGD treated astrocytes and hamper the protective effect of DEX in cell apoptosis (P < 0.05), suggesting that DEX and JAK/STAT signal pathway inhibits OGD induced apoptosis in astrocytes by down-regulating JMJD3. CONCLUSION: DEX protects astrocytes against apoptosis via inhibiting JAK2/STAT3 signal pathway and downregulating JMJD3 expression in vitro.
OBJECTIVE: There is an increasing interest concerning the contribution of astrocytes to the intrinsic bioremediation of ischemic brain injury. The aim of this work was to disclose the effects and mechanism of dexmedetomidine (DEX) on the apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. METHODS: Primary cultured astrocytes separated from Sprague-Dawley (SD) rats were subjected to OGD treatment. Astrocytes were transfected with si-JMJD3 or pcDNA3.1-JMJD3 and then treated with DEX or JAK/STAT inhibitor (WP1066) before cell apoptosis was detected by TUNEL apoptosis kit. Western blot was applied to assess the level of apoptosis-related proteins Caspase-3, Bax and Bcl-2. Astrocyte cell viability was assessed by measuring the lactate dehydrogenase (LDH) level using a LDH assay kit. RESULTS: Astrocytes received OGD treatment had increased LDH and elevated apoptotic rate (P < 0.05). DEX could suppress OGD induced cytotoxic effect on astrocytes, as evidenced by decreased LDH release and suppressed cell apoptosis rate (P < 0.05). Meanwhile, DEX and WP1066 treatment were also found to inhibit the phosphorylation level of STAT1 and STAT3 (P < 0.05), indicating the DEX could suppress the activation of JAK/STAT signal pathway. JMJD3 overexpression in astrocytes could suppress the anti-apoptotic function of WP1066 in OGD treated astrocytes and hamper the protective effect of DEX in cell apoptosis (P < 0.05), suggesting that DEX and JAK/STAT signal pathway inhibits OGD induced apoptosis in astrocytes by down-regulating JMJD3. CONCLUSION:DEX protects astrocytes against apoptosis via inhibiting JAK2/STAT3 signal pathway and downregulating JMJD3 expression in vitro.