TY - JOUR
T1 - Reactive sulfur species impair Ca2+/calmodulin-dependent protein kinase II via polysulfidation
AU - Araki, Shoma
AU - Takata, Tsuyoshi
AU - Tsuchiya, Yukihiro
AU - Watanabe, Yasuo
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas "Oxygen Biology: a new criterion for integrated understanding of life" [No. 26111008 ] (Y.W.); JSPS KAKENHI Grants-in-Aid for Scientific Research C [No. 18K11083 ] (Y.W.); Young Scientists [No. 18K14853 ] (T.T.); Young Scientists B [No. 15K18994 ] (Y.T.); Program for the Strategic Research Foundation at Private Universities [No. S1311012 ] (Y·W.) of the MEXT, Japan ; Grant-in-Aid from the Showa Pharmaceutical University for Young Scientists (T.T.), (Y.T.); and Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (S.A.).
Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas ?Oxygen Biology: a new criterion for integrated understanding of life? [No. 26111008] (Y.W.); JSPS KAKENHI Grants-in-Aid for Scientific Research C [No. 18K11083] (Y.W.); Young Scientists [No. 18K14853] (T.T.); Young Scientists B [No. 15K18994] (Y.T.); Program for the Strategic Research Foundation at Private Universities [No. S1311012] (Y?W.) of the MEXT, Japan; Grant-in-Aid from the Showa Pharmaceutical University for Young Scientists (T.T.), (Y.T.); and Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (S.A.).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/1/8
Y1 - 2019/1/8
N2 - We previously reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is inhibited by S-nitrosylation of Cys6 in cells. Herein, we show that polysulfidation of CaMKII at Cys6 limits its enzyme activity following reactive sulfur species (RSS) stimulus. In vitro incubation of CaMKII with the RSS donor, Na2S4, induced the inhibition of the enzyme via its polysulfidation. Treatment with dithiothreitol reversed the polysulfidation and the subsequent inhibition. The inhibition of CaMKII by Na2S4 is competitive with ATP but not with the peptide substrate Syntide-2. In transfected cells expressing CaMKII, the enzyme activity decreased upon treatment with Na2S4, whereas cells expressing mutant CaMKII (C6A) were resistant to this treatment. In addition, the endogenous CaMKII was inhibited by treatment with Na2S4 in RAW264.7 murine macrophage cells. These results suggest a novel regulation of CaMKII by RSS via its Cys6 polysulfidation in cells.
AB - We previously reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is inhibited by S-nitrosylation of Cys6 in cells. Herein, we show that polysulfidation of CaMKII at Cys6 limits its enzyme activity following reactive sulfur species (RSS) stimulus. In vitro incubation of CaMKII with the RSS donor, Na2S4, induced the inhibition of the enzyme via its polysulfidation. Treatment with dithiothreitol reversed the polysulfidation and the subsequent inhibition. The inhibition of CaMKII by Na2S4 is competitive with ATP but not with the peptide substrate Syntide-2. In transfected cells expressing CaMKII, the enzyme activity decreased upon treatment with Na2S4, whereas cells expressing mutant CaMKII (C6A) were resistant to this treatment. In addition, the endogenous CaMKII was inhibited by treatment with Na2S4 in RAW264.7 murine macrophage cells. These results suggest a novel regulation of CaMKII by RSS via its Cys6 polysulfidation in cells.
KW - Ca/calmodulin-dependent protein kinase (CaMK)
KW - Phosphorylation
KW - Polysulfidation
KW - Reactive sulfur species (RSS)
KW - Redox regulation
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U2 - 10.1016/j.bbrc.2018.11.134
DO - 10.1016/j.bbrc.2018.11.134
M3 - Article
C2 - 30509490
AN - SCOPUS:85057482153
VL - 508
SP - 550
EP - 555
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -