Yao Shen1, Yueyang Tian2, Jianbo Yang2, Xiaojie Shi2, Li Ouyang2, Jieqiong Gao2, Jianxin Lu3. 1. Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: yueshen-2002@163.com. 2. Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. 3. Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: jxlu313@163.com.
Abstract
OBJECTIVE: The aim of this study was to investigate the effects of carnosine on the bioenergetic profile of cultured cortical astrocytes under normal and ischemic conditions. METHODS: The Seahorse Bioscience XF96 Extracellular Flux Analyzer was used to measure the oxygen consumption rates (OCRs) and extracellular acidification rates (ECARs) of cultured cortical astrocytes treated with and without carnosine under normal and ischemic conditions. RESULTS: Under the normal growth condition, the basal OCRs and ECARs of astrocytes were 21.72±1.59 pmol/min/μg protein and 3.95±0.28 mpH/min/μg protein respectively. Mitochondrial respiration accounted for ~80% of the total cellular respiration and 85% of this coupled to ATP synthesis. Carnosine significantly reduced basal OCRs and ECARs and ATP-linked respiration, but it strikingly increased the spare respiratory capacity of astrocytes. The cellular ATP level in carnosine-treated astrocytes was reduced to ~42% of the control. However, under the ischemic condition, carnosine upregulated the mitochondrial respiratory and cellular ATP content of astrocytes exposed to 8h of oxygen-glucose deprivation (OGD) followed by 24 h of recovery under the normal growth condition. CONCLUSIONS: Carnosine may be an endogenous regulator of astrocyte energy metabolism and a clinically safe therapeutic agent for promoting brain energy metabolism recovery after ischemia/reperfusion injury.
OBJECTIVE: The aim of this study was to investigate the effects of carnosine on the bioenergetic profile of cultured cortical astrocytes under normal and ischemic conditions. METHODS: The Seahorse Bioscience XF96 Extracellular Flux Analyzer was used to measure the oxygen consumption rates (OCRs) and extracellular acidification rates (ECARs) of cultured cortical astrocytes treated with and without carnosine under normal and ischemic conditions. RESULTS: Under the normal growth condition, the basal OCRs and ECARs of astrocytes were 21.72±1.59 pmol/min/μg protein and 3.95±0.28 mpH/min/μg protein respectively. Mitochondrial respiration accounted for ~80% of the total cellular respiration and 85% of this coupled to ATP synthesis. Carnosine significantly reduced basal OCRs and ECARs and ATP-linked respiration, but it strikingly increased the spare respiratory capacity of astrocytes. The cellular ATP level in carnosine-treated astrocytes was reduced to ~42% of the control. However, under the ischemic condition, carnosine upregulated the mitochondrial respiratory and cellular ATP content of astrocytes exposed to 8h of oxygen-glucose deprivation (OGD) followed by 24 h of recovery under the normal growth condition. CONCLUSIONS: Carnosine may be an endogenous regulator of astrocyte energy metabolism and a clinically safe therapeutic agent for promoting brain energy metabolism recovery after ischemia/reperfusion injury.
Authors: Levy W Macedo; José H Cararo; Soliany G Maravai; Cinara L Gonçalves; Giovanna M T Oliveira; Luiza W Kist; Camila Guerra Martinez; Eleonora Kurtenbach; Maurício R Bogo; Alan R Hipkiss; Emilio L Streck; Patrícia F Schuck; Gustavo C Ferreira Journal: Mol Neurobiol Date: 2015-10-17 Impact factor: 5.590
Authors: Yao Lu; Su Li; Hengfang Wu; Zhiping Bian; Jindan Xu; Chunrong Gu; Xiangjian Chen; Di Yang Journal: Int J Mol Med Date: 2015-09-15 Impact factor: 4.101