Persulfide Signaling in Stress-Initiated Calmodulin Kinase Response

Takata, Tsuyoshi; Araki, Shoma; Tsuchiya, Yukihiro; Watanabe, Yasuo

doi:10.1089/ars.2020.8138

Cited by 10 publications

(11 citation statements)

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“…Protein persulfides (i.e., protein S-sulfhydration or persulfidation; Figure 1 ) have been found in various proteins [ 5 , 6 , 37 , 38 , 39 ]. Accumulating evidence suggests that protein persulfidation may have an important role in regulating protein functions [ 17 , 18 , 40 , 41 , 42 ]. Previous studies reported that protein persulfides were formed as a result of the post-translational modification of thiols that were mediated by certain sulfur-donating molecules such as H 2 S [ 43 , 44 , 45 ].…”

Section: Biosynthesis Of Cysssh and Related Moleculesmentioning

confidence: 99%

“…Takahashi et al demonstrated that CysSSH is involved in the regulation of tRNA methylthiolation and insulin secretion [ 16 ]. Calcium signaling mediated by Ca 2+ /calmodulin-dependent kinase I (CaMK I) can be regulated by protein sulfhydration at Cys179 [ 17 , 18 ]. CaMK I is activated by phosphorylation at Thr177, which is irreversibly inhibited by Cys177 persulfhydration [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Calcium signaling mediated by Ca 2+ /calmodulin-dependent kinase I (CaMK I) can be regulated by protein sulfhydration at Cys179 [ 17 , 18 ]. CaMK I is activated by phosphorylation at Thr177, which is irreversibly inhibited by Cys177 persulfhydration [ 17 , 18 ]. Recent studies reported that CysSSH can participate in energy metabolism as it functions in sulfur respiration in mitochondria [ 3 , 4 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Biomolecules 2020, 10, x FOR PEER REVIEW 2 of 13 regulated by protein sulfhydration at Cys179 [17,18]. CaMK I is activated by phosphorylation at Thr177, which is irreversibly inhibited by Cys177 persulfhydration [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic Regulation and Biological Functions of Reactive Cysteine Persulfides and Polysulfides

et al. 2020

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Cysteine persulfide (CysSSH) and cysteine polysulfides (CysSSnH, n > 1) are cysteine derivatives that have sulfane sulfur atoms bound to cysteine thiol. Advances in analytical methods that detect and quantify persulfides and polysulfides have shown that CysSSH and related species such as glutathione persulfide occur physiologically and are prevalent in prokaryotes, eukaryotes, and mammals in vivo. The chemical properties and abundance of these compounds suggest a central role for reactive persulfides in cell-regulatory processes. CysSSH and related species have been suggested to act as powerful antioxidants and cellular protectants and may serve as redox signaling intermediates. It was recently shown that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase. In addition, we discovered that CARS is involved in protein polysulfidation that is coupled with translation. Mitochondrial activity in biogenesis and bioenergetics is supported and upregulated by CysSSH derived from mitochondrial CARS. In this review article, we discuss the mechanisms of the biosynthesis of CysSSH and related persulfide species, with a particular focus on the roles of CARS. We also review the antioxidative and anti-inflammatory actions of persulfides.

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Section: Biosynthesis Of Cysssh and Related Moleculesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enzymatic Regulation and Biological Functions of Reactive Cysteine Persulfides and Polysulfides

et al. 2020

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“…S-nitrosylation and polysulfidation have similar mechanisms and occurred at acid-base motif [97]. Aside from S-nitrosylation of CaMKII at Cys6, it was recently reported that CaMKII is sensitive to inhibition by RSS through polysulfidation at Cys6, being competitive with ATP [98,99]. Cys30 is also polysulfidated by RSS but C30A mutant of CaMKII is inhibited by RSS with ATP competitive fashion (our unpublished data).…”

Section: Discussionmentioning

confidence: 67%

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

Araki

Osuka

Takata

et al. 2020

IJMS

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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.

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