2019
DOI: 10.1126/scisignal.aaw1920
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Abstract: Chronic exposure to methylmercury (MeHg), an environmental electrophilic pollutant, reportedly increases the risk of human cardiac events. We report that exposure to a low, non-neurotoxic dose of MeHg precipitated heart failure induced by pressure overload in mice. Exposure to MeHg at 10 ppm did not induce weight loss typical of higher doses but caused mitochondrial hyperfission in myocardium through the activation of Drp1 by its guanine nucleotide exchange factor filamin-A. Treatment of neonatal rat cardiomyo… Show more

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Cited by 26 publications
(22 citation statements)
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References 51 publications
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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%
“…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%
“…(53) Treatment with sodium hydrosulfide, a donor for reactive polysulfides, reversed the MeHg-mediated Drp1 depolysulfidation and the associated vulnerability to mechanical load in rodent and human cardiomyocytes, and mouse hearts. (53) Thus, exposure to harsh exogenous electrophiles, such as MeHg, disrupts endogenous persulfide-dependent redox signal regulation, which may be a critical event in the pathogenesis of neurodegenerative diseases and cardiac dysfunction (Fig. 3).…”
Section: Disruption Of the Persulfide-dependent Regulation Of Redox Smentioning
confidence: 99%
“…(10) Pretreatment with sodium tetrasulfide, a polysulfide donor, significantly inhibited the MeHg-induced accumulation of endogenous 8-nitro-cGMP and attenuated the neuronal cell death caused by MeHg exposure. (10) In addition, Nishimura et al (53) demonstrated that exposure to a sub-neurotoxic dose of MeHg (10 ppm), which reportedly does not affect neuronal functions in mice over the course of one year, (54) induced depolysulfidation of dynamin-related protein 1 (Drp1), resulting in an increased cardiac fragility to mechanical load through filamin-dependent mitochondrial hyperfission after pressure overload in mouse hearts. (53) Treatment with sodium hydrosulfide, a donor for reactive polysulfides, reversed the MeHg-mediated Drp1 depolysulfidation and the associated vulnerability to mechanical load in rodent and human cardiomyocytes, and mouse hearts.…”
Section: Disruption Of the Persulfide-dependent Regulation Of Redox Smentioning
confidence: 99%
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“…Cardiac remodeling is characterized by structural and morphological changes of the heart, including hypertrophy and fibrosis, and is a major clinical outcome of heart failure after cardiac injury 1 , 2 . Structural remodeling is thought to be a plasticity process of the heart to overcome hemodynamic overload, but cardiac resistance (i.e., robustness) to mechanical stress may be reduced by additional environmental factors, such as physical and chemical stresses 3 .…”
Section: Introductionmentioning
confidence: 99%