title: Carnosine modulates glutamine synthetase expression in senescent astrocytes exposed to oxygen-glucose deprivation/recovery.
abstract: Carnosine is believed to be neuroprotective in cerebral ischemia. However, few reports concern its function on senescent astrocytes during cerebral ischemia. The aim of this study was to investigate the effects of carnosine on cell damage and glutamine synthetase (GS) expression in D-galactose-induced senescent astrocytes exposed to oxygen-glucose deprivation/recovery (OGD/R). The results showed that OGD/R caused massive cell damage and a significant decrease in GS expression both in the young and senescent astrocytes. The GS expression level was partly recovered whereas it continued to decline in the recovery stage in the young and senescent astrocytes, respectively. Decreased GS expression significantly inhibited glutamate uptake and glutamine production and release. Carnosine prevented the cell damage, rescued the expression of GS and reversed the glutamate uptake activity and glutamine production in the senescent astrocytes exposed to OGD/R. The modulatory effect of carnosine on GS expression was partly antagonized by pyrilamine, a selective histamine H1receptors antagonist, but not bestatin. Bisindolylmaleimide II, a broad-spectrum inhibitor of PKC could also reverse the action of carnosine on GS expression. Thus, histamine H1receptors and PKC pathway may be involved in the modulatory action of carnosine in GS expression in the senescent astrocytes exposed to OGD/R.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Shi
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Cao
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: yueshen-2002@163.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lyu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D002336:Carnosine / Q000008:administration & dosage*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D005947:Glucose / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D002336:Carnosine; D005974:Glutamate-Ammonia Ligase; D005947:Glucose; D010100:Oxygen
keywords: Carnosine; Glutamine synthetase (GS); Histamine H1 receptor; Oxygen-glucose deprivation/recovery (OGD/R); Protein kinase C; Senescent astrocyte