Supersulfide catabolism participates in maladaptive remodeling of cardiac cells

Journal of Pharmacological Sciences, Год журнала: 2024, Номер 155(4), С. 121 - 130

Опубликована: Май 21, 2024

The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, well interstitial fibrosis. Conversely, myocardial hypertrophy hemodynamic loading perceived compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, two or more sulfur atoms catenated in normal hearts, supersulfide catabolism pathologic hearts after infarction correlated worsened prognosis failure. However, impact on remains unclear. Here, we investigated involvement metabolism cardiomyocyte remodeling, using a model adenosine 5'-triphosphate (ATP) receptor-stimulated atrophy endothelin-1 neonatal rat cardiomyocytes. Results revealed contrasting changes intracellular its catabolite, hydrogen sulfide (H

Язык: Английский

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Capture of Electrophilic Quinones in the Extracellular Space: Evidence for a Phase Zero Reaction

Chemical Research in Toxicology, Год журнала: 2022, Номер 36(1), С. 23 - 31

Опубликована: Дек. 16, 2022

Electrophilic quinones are produced during the combustion of gasoline in atmosphere. Although these reactive species covalently bind to protein-based nucleophiles cells, resulting formation protein adducts involved modulation redox signaling pathways and cytotoxicity, extracellular regulation is not understood. In this study, incubation 1,2-naphthoquinone (1,2-NQ) with low-molecular-weight fraction mouse plasma resulted consumption cysteine (CysSH) a concentration-dependent manner. Covalent modification albumin was markedly repressed by addition either or CysSH, suggesting that CysSH protects forming conjugate 1,2-NQ. Similar phenomena also occurred for other atmospheric 1,4-NQ 1,4-benzoquinone (1,4-BQ). The cystine culture medium without amino acids enhanced release from A431 cells blocked 1,2-NQ-mediated arylation intracellular proteins, 1,2-NQ interacts CysSH. Liquid chromatography-tandem mass spectrometry analysis revealed 1,4-BQ undergoes nucleophilic attack yielding 1,2-NQH2-SCys adduct 1,4-BQH2-SCys adduct, respectively. Unlike 1,4-BQ, authentic had little effect on covalent cellular proteins viability cells. These results suggest electrophilic readily trapped released less-toxic thereby repressing proteins. findings provide evidence existence "phase zero" reaction electrophiles prior their uptake

Язык: Английский

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Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation inVibrio cholerae

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 13, 2023

The vertebrate host’s immune system and resident commensal bacteria deploy a range of highly reactive small molecules that provide barrier against infections by microbial pathogens. Gut pathogens, such as Vibrio cholerae , sense respond to these stressors modulating the expression exotoxins are crucial for colonization. Here, we employ mass-spectrometry-based profiling, metabolomics, assays biophysical approaches show transcriptional activation hemolysin gene hlyA in V. is regulated intracellular sulfur species (RSS), specifically sulfane sulfur. We first present comprehensive sequence similarity network analysis arsenic repressor (ArsR) superfamily regulators where RSS oxygen (ROS) sensors segregate into distinct clusters. HlyU, activator belongs RSS-sensing cluster readily reacts with organic persulfides, showing no reactivity remaining DNA-bound following treatment various ROS vitro, including H 2 O . Surprisingly, cell cultures, both sulfide peroxide downregulate HlyU-dependent However, metabolite profiling shows raise endogenous inorganic disulfide levels similar extent, accounting this crosstalk, confirming attenuates HlyU-mediated specific response RSS. These findings new evidence gut pathogens may harness an evolutionary adaptation allows them overcome inflammatory exotoxins.

Язык: Английский

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Multi-defense Pathways against Electrophiles through Adduct Formation by Low Molecular Weight Substances with Sulfur Atoms

Toxicological Sciences, Год журнала: 2024, Номер unknown

Опубликована: Окт. 7, 2024

There is a variety of electrophiles in the environment. In addition, there are precursor chemicals that undergo metabolic activation by enzymes and conversion to body. Although covalently bind protein nucleophiles, they also form adducts associated with adaptive or toxic responses. Low molecular weight compounds containing sulfur capable blocking such adduct formation capturing electrophiles. this review, we present out findings on capture inactivation 1) intracellular glutathione, 2) reactive species 3) extracellular cysteine (formed during production adducts). These actions not only substantially suppress electrophilic activity but regulate formation.

Язык: Английский

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