title: Activation of the calcium-sensing receptor promotes apoptosis by modulating the JNK/p38 MAPK pathway in focal cerebral ischemia-reperfusion in mice.
abstract: Exact mechanism of cerebral ischemic stroke remains unclear. The calcium-sensing receptor (CaSR), a G-protein coupled receptor, has been reported to participate in the pathology of myocardial ischemia-reperfusion (I/R) injury and myocardial hypertrophy. Nevertheless, only a limited number of studies have been conducted to investigate the role of CaSR in cerebral ischemic stroke. This study was to investigate the effect of CaSR activation on cerebral ischemic stroke. Male adult Kunming mice were subjected to 2-h focal cerebral ischemia followed by 22-h reperfusion. Then, the brain was collected, and the expression of CaSR, JNK, p38, Bcl-2, and Bax was detected by Western blot assay. The morphology of neurons in the brain was evaluated by HE staining. Neurological function was scored, and the infarct volume was determined by TTC (triphenyltetrazolium chloride) staining. Results showed that ischemia/reperfusion (I/R) increased CaSR expression and induced neuronal apoptosis in the brain. Gadolinium trichloride (GdCl3), an agonist of CaSR, further deteriorated neurological dysfunction, increased infarct volume, enhanced CaSR expression, and promoted neuronal apoptosis. In addition, GdCl3 unregulated expression of Bax, p-JNK, and p-p38, and down-regulated Bcl-2 expression during I/R, which were attenuated by NPS2390, an inhibitor of CaSR. In conclusion, the CaSR activation promotes apoptosis in focal cerebral I/R in mice, which may be related to the activation of JNK/p38 MAPK signalling pathway. Targeting CaSR may be a novel strategy for the prevention and treatment of cerebral ischemic stroke.
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Ministry of Education, Key Laboratory of Chinese Medicine Research and Development of State Administration of Traditional Chinese Medicine, Anhui Medical University Hefei 230032, China.
authors.forename: Yilan
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Ministry of Education, Key Laboratory of Chinese Medicine Research and Development of State Administration of Traditional Chinese Medicine, Anhui Medical UniversityHefei 230032, China; Department of Medical, Tongling PolytechnicTongling 244000, China.
authors.forename: Caijuan
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Otorhinolaryngology, Anhui Provincial Hospital Hefei, Anhui 230001, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Ministry of Education, Key Laboratory of Chinese Medicine Research and Development of State Administration of Traditional Chinese Medicine, Anhui Medical University Hefei 230032, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Ministry of Education, Key Laboratory of Chinese Medicine Research and Development of State Administration of Traditional Chinese Medicine, Anhui Medical University Hefei 230032, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Ministry of Education, Key Laboratory of Chinese Medicine Research and Development of State Administration of Traditional Chinese Medicine, Anhui Medical University Hefei 230032, China.
authors.forename: Liuyi
authors.initials: L
authors.lastname: Dong
keywords: Calcium-sensing receptor (CaSR); MAPK; apoptosis; focal cerebral ischemia-reperfusion; mice