OBJECTIVES: This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. METHODS: Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. RESULTS: Autophagy and ER stress were enhanced in the week after ICH. At 6 hours after ICH, autophagy was excessive, while the autophagic flux was damaged at 72 hours and return to be intact at 7 days after ICH. At 6 hours after ICH, ER stress induction by TM could enhance autophagy and lead to caspase 12-mediated apoptosis and neuronal degeneration, which was further aggravated by autophagy induction. At 7 days after ICH, ER stress inhibition by TUDCA still could suppress ICH-induced SBI. And, the effects of TUDCA were enhanced by autophagy induction. CONCLUSIONS: At 6 hours after ICH, excessive autophagy may participate in ER stress-induced brain injury; at 7 days after ICH, autophagy could enhance the protection of ER stress inhibitor possibly via clearing up the cell rubbish generated due to the early-stage damaged autophagic flux.
OBJECTIVES: This study aimed to evaluate the roles of autophagy and endoplasmic reticulum (ER) stress in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) in rats. METHODS: Autophagy inducer (rapamycin) and inhibitor (3-methyladenine), as well as ER stress activator (tunicamycin, TM) and inhibitor (tauroursodeoxycholic acid, TUDCA), were used. Bafilomycin A1, an inhibitor of autophagosome-lysosome fusion, was used to assess autophagic flux. RESULTS: Autophagy and ER stress were enhanced in the week after ICH. At 6 hours after ICH, autophagy was excessive, while the autophagic flux was damaged at 72 hours and return to be intact at 7 days after ICH. At 6 hours after ICH, ER stress induction by TM could enhance autophagy and lead to caspase 12-mediated apoptosis and neuronal degeneration, which was further aggravated by autophagy induction. At 7 days after ICH, ER stress inhibition by TUDCA still could suppress ICH-induced SBI. And, the effects of TUDCA were enhanced by autophagy induction. CONCLUSIONS: At 6 hours after ICH, excessive autophagy may participate in ER stress-induced brain injury; at 7 days after ICH, autophagy could enhance the protection of ER stress inhibitor possibly via clearing up the cell rubbish generated due to the early-stage damaged autophagic flux.
Authors: Wan-Young Kim; Sun Ah Nam; Ho Cheol Song; Jun Sung Ko; Sang Hee Park; Hong Lim Kim; Euy Jin Choi; Yong-Soo Kim; Jin Kim; Yong Kyun Kim Journal: Nephrology (Carlton) Date: 2012-02 Impact factor: 2.506
Authors: Bing Jiang; Lin Li; Qianwei Chen; Yihao Tao; Liming Yang; Bo Zhang; John H Zhang; Hua Feng; Zhi Chen; Jun Tang; Gang Zhu Journal: Transl Stroke Res Date: 2016-11-03 Impact factor: 6.829