Phosphorylation by calcium calmodulin-dependent protein kinase II and protein kinase C modulates the activity of nitric oxide synthase

1991 ◽  
Vol 180 (3) ◽  
pp. 1396-1402 ◽  
Author(s):  
Masaki Nakane ◽  
Jane Mitchell ◽  
Ulrich Förstermann ◽  
Ferid Murad
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Kinase C ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Oxide Synthase

scholarly journals Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons

2020 ◽  
Vol 21 (21) ◽  
pp. 7997
Author(s):  
Shoma Araki ◽  
Koji Osuka ◽  
Tsuyoshi Takata ◽  
Yukihiro Tsuchiya ◽  
Yasuo Watanabe
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Cell Injury ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Pathophysiological Role ◽  
Protein Kinase Ii ◽  
Mutual Regulation ◽  
Dependent Protein ◽  
Oxide Synthase

Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is highly abundant in the brain and exhibits broad substrate specificity, thereby it is thought to participate in the regulation of neuronal death and survival. Nitric oxide (NO), produced by neuronal NO synthase (nNOS), is an important neurotransmitter and plays a role in neuronal activity including learning and memory processes. However, high levels of NO can contribute to excitotoxicity following a stroke and neurodegenerative disease. Aside from NO, nNOS also generates superoxide which is involved in both cell injury and signaling. CaMKII is known to activate and translocate from the cytoplasm to the post-synaptic density in response to neuronal activation where nNOS is predominantly located. Phosphorylation of nNOS at Ser847 by CaMKII decreases NO generation and increases superoxide generation. Conversely, NO-induced S-nitrosylation of CaMKII at Cys6 is a prominent determinant of the CaMKII inhibition in ATP competitive fashion. Thus, the “cross-talk” between CaMKII and NO/superoxide may represent important signal transduction pathways in brain. In this review, we introduce the molecular mechanism of and pathophysiological role of mutual regulation between CaMKII and nNOS in neurons.

scholarly journals Neuronal Protection and Preservation of Calcium/Calmodulin-Dependent Protein Kinase II and Protein Kinase C Activity by Dextrorphan Treatment in Global Ischemia

1993 ◽  
Vol 13 (4) ◽  
pp. 550-557 ◽  
Author(s):  
Jaroslaw Aronowski ◽  
M. Neal Waxham ◽  
James C. Grotta
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Neuronal Morphology ◽  
Global Ischemia ◽  
Specific Substrate ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Kinase C ◽  
Protein Kinase Ii ◽  
Dependent Protein

This study analyzed the ability of the N-methyl-d-aspartate receptor antagonist dextrorphan (DX) to prevent neuronal degeneration (analyzed by light microscopy), calmodulin (CaM) redistribution (analyzed by immunocytochemistry) and changes in activity of two major Ca2+-dependent protein kinases—calcium/calmodulin-dependent protein kinase II (CaM-KII) and protein kinase C (PKC) (analyzed by specific substrate phosphorylation) after 20 min of global ischemia (four-vessel occlusion model) in rats. DX treatment before and after ischemia significantly protected hippocampal and cortical neurons from neurodegeneration whereas DX posttreatment alone did not have any effect on preservation of neuronal morphology as compared with placebo treatment analyzed 72 h after 20 min of ischemia. Similarly to histological changes, DX exhibited protection against redistribution of CaM observed after ischemia. These changes were detected both in hippocampus as well as in cerebral cortex. Finally, DX administered before ligation of the carotid arteries reduced loss in both CaM-KII and PKC activity evoked by ischemia.

Abstract P076: Essential Role of Neuronal Nitric Oxide Synthase in Ca 2+ /Calmodulin-Dependent Protein Kinase II Activation in Cardiac Myocytes During β-Adrenergic Stimulation

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Lifei Tang ◽  
Steve Roof ◽  
Mark Ziolo
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Dependent Protein Kinase ◽  
Positive Inotropy ◽  
Cell Shortening ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Oxide Synthase

RATIONALE: Stimulation of the beta-adrenergic (beta-AR) pathway leads to positive inotropy, and is the major regulator of heart function. In addition to the traditional PKA pathway, activation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and neuronal nitric oxide synthase (NOS1) signaling also play important roles in the positive inotropy by modulating ryanodine receptor (RyR) activity. OBJECTIVE: The upstream activators of CaMKII during beta-AR stimulation are not well defined. The purpose of this study is to investigate if there is any cross-talk between the CaMKII and NOS1 signaling pathways. METHODS AND RESULTS: Myocytes were isolated from wildtype (WT, C57Bl/6) and NOS1 −/− mice. Ca 2+ transients (Fluo-4) and cell shortening (edge detection) were simultaneously measured. RyR activity was measured using the SR Ca 2+ leak/load relationship. CaMKII was acutely inhibited by KN93. In WT myocytes, KN93 decreased beta-AR stimulated contraction (Ca2+ transients (Fluo-4) and cell shortening). In NOS1 −/− myocytes, beta-AR stimulated contraction was blunted compared to WT, and KN93 had no further effect on contraction. Furthermore, beta-AR stimulated RyR activity was blunted in NOS1 −/− compared to WT myocytes. As with contraction, KN93 decreased beta-AR stimulated RyR activity in WT myocytes, but had no effect in NOS1 −/− myocytes. CONCLUSION: These data suggest that NOS1 is required for CaMKII-mediated RyR activation which contributes to positive inotropy during beta-AR stimulation. Further study of this pathway is warranted since CAMKII expression and activity are increased in cardiac hypertrophy and heart failure. A better understanding of the NOS1/CaMKII pathway during beta-AR stimulation has beneficial therapeutic potential for heart diseases.

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