title: Protein kinase C-β mediates neuronal activation of Na(+)/H(+) exchanger-1 during glutamate excitotoxicity.
abstract: Na(+)/H(+) exchanger-1 (NHE-1) activity is known to play a critical role in the neuronal injury caused by glutamate. However, the underlying mechanism is not clear. This study shows that NHE-1 activation and its phosphorylation during glutamate exposure were attenuated by the inhibition of protein kinase C (PKC)-βI and -βII, leading to reduced neuronal death. In addition, activations of PKC-βI and -βII by PKC-βI and -βII CAT plasmid or by PMA, PKC-β pharmacological activator have stimulated the activity and phosphorylation of NHE-1, which were abolished by inhibition of PKC-β in neuronal cells. Furthermore, the inhibition of PKC-β has mediated neuroprotective effect on glutamate-induced cells, which is similar to neuroprotective efficacy of siRNA NHE-1 transfection. Taken together, these results suggest that activation of the PKC-βI and -βII pathway by glutamate increases the activity and phosphorylation of NHE-1, and that these increases contribute to neuronal cell death. In this study, we demonstrate that PKC-βI and -βII are involved in the regulation of NHE-1 activation following glutamate exposure in neuron.
authors.affiliation: College of Pharmacy, Ajou University, 206, Worldcup-ro, Yeongtong-gu, Suwon 443-749, Republic of Korea. Electronic address: pfiffer@ajou.ac.kr.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Yonsei University, College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Electronic address: osalive@yuh.ac.
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Yoon
authors.affiliation: Department of Pharmacology, Yonsei University, College of Medicine, 50, Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea. Electronic address: mlee@yuh.ac.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Ajou University, 206, Worldcup-ro, Yeongtong-gu, Suwon 443-749, Republic of Korea; Research Institute of Pharmaceutical Sciences and Technology, Ajou University, 206, Worldcup-ro, Yeongtong-gu, Suwon 443-749, Republic of Korea. Electronic address: yisjung@ajou.ac.kr.
authors.forename: Yi-Sook
authors.initials: YS
authors.lastname: Jung
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D010703:Phorbol Esters; D034741:RNA, Small Interfering; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; C119222:phorbol-12-myristate; D018698:Glutamic Acid; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D064546:Protein Kinase C beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Glutamate; Na(+)/H(+) exchanger; Neuroprotection; Phosphorylation; Protein Kinase C-β