PMID- 31539160
OWN - NLM
STAT- MEDLINE
DCOM- 20201006
LR  - 20201006
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 17
DP  - 2019 Sep
TI  - Denitrosylation of nNOS induced by cerebral ischemia-reperfusion contributes to 
      nitrosylation of CaMKII and its inhibition of autophosphorylation in hippocampal 
      CA1.
PG  - 7674-7683
LID - 18891 [pii]
LID - 10.26355/eurrev_201909_18891 [doi]
AB  - OBJECTIVE: The aim of this study is to investigate the relation between CaMKII 
      S-nitrosylation and its activation, as well as the underlying mechanism, after 
      global cerebral ischemia-reperfusion. MATERIALS AND METHODS: The rat model of 
      cerebral ischemia-reperfusion was established by four-vessel occlusion of 15 min 
      and reperfusion of different times. nNOS inhibitor 7-nitroindazole (7-NI), 
      exogenous nitric oxide donor GSNO (nitrosoglutathione), or N-methyl-D-aspartate 
      receptor (NMDAR) antagonist MK-801 were administered before ischemia. The 
      expressions of S-nitrosylation and phosphorylation of CaMKII and nNOS were 
      detected by biotin switch assay, immunoblotting, and immunohistochemical staining 
      after cerebral ischemia-reperfusion. The survival of hippocampal CA1 pyramidal 
      cells after administration of the three drugs was examined by cresyl violet 
      staining. RESULTS: Following cerebral ischemia-reperfusion, the S-nitrosylation 
      of CaMKII was increased, accompanied by a decrease of phosphorylation, suggesting 
      a decrease of activity (p<0.05). Meanwhile, the phosphorylation and 
      S-nitrosylation of nNOS were notably decreased at the same time point (p<0.05). 
      The administration of 7-NI, GSNO, and MK-801 increased the S-nitrosylation and 
      phosphorylation of nNOS, leading to the attenuation of increased S-nitrosylation 
      and decreased autophosphorylation of CaMKII after cerebral ischemia-reperfusion 
      (p<0.05). Administration of MK-801, GSNO, and 7-NI significantly decreased the 
      neuronal damage in rat hippocampal CA1 caused by cerebral ischemia-reperfusion 
      (p<0.05). CONCLUSIONS: After cerebral ischemia-reperfusion, the decrease of 
      autophosphorylation of CaMKII regulated by its S-nitrosylation may be due to the 
      denitrosylation of nNOS and subsequent NO production. Increasing the 
      phosphorylation of CaMKII by nNOS inhibitor, exogenous NO donor or NMDA receptor 
      antagonist exerted neuroprotective effects against cerebral ischemia-reperfusion 
      injury.
FAU - Yu, L-M
AU  - Yu LM
FAU - Zhang, T-Y
AU  - Zhang TY
AD  - Research Center of Biochemistry and Molecular Biology and Jiangsu Key Laboratory 
      of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, 
      China. lichong_xzhmu@sina.com.
FAU - Yin, X-H
AU  - Yin XH
FAU - Yang, Q
AU  - Yang Q
FAU - Lu, F
AU  - Lu F
FAU - Yan, J-Z
AU  - Yan JZ
FAU - Li, C
AU  - Li C
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Indazoles)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 57564-91-7 (S-Nitrosoglutathione)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - UX0N37CMVH (7-nitroindazole)
SB  - IM
MH  - Animals
MH  - CA1 Region, Hippocampal/*metabolism/pathology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Disease Models, Animal
MH  - Dizocilpine Maleate/pharmacology
MH  - Indazoles/pharmacology
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type I/antagonists & inhibitors/*metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/metabolism/*pathology
MH  - S-Nitrosoglutathione/pharmacology
EDAT- 2019/09/21 06:00
MHDA- 2020/10/07 06:00
CRDT- 2019/09/21 06:00
PHST- 2019/09/21 06:00 [entrez]
PHST- 2019/09/21 06:00 [pubmed]
PHST- 2020/10/07 06:00 [medline]
AID - 18891 [pii]
AID - 10.26355/eurrev_201909_18891 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7674-7683. doi: 
      10.26355/eurrev_201909_18891.