Sodium hydrosulphide restores tumour necrosis factor‐α‐induced mitochondrial dysfunction and metabolic dysregulation in HL‐1 cells

Abstract

Tumour necrosis factor (TNF)‐α induces cardiac metabolic disorder and mitochondrial dysfunction. Hydrogen sulphide (H2S) contains anti‐inflammatory and biological effects in cardiomyocytes. This study investigated whether H2S modulates TNF‐α‐dysregulated mitochondrial function and metabolism in cardiomyocytes. HL‐1 cells were incubated with TNF‐α (25 ng/mL) with or without sodium hydrosulphide (NaHS, 0.1 mmol/L) for 24 hours. Cardiac peroxisome proliferator‐activated receptor (PPAR) isoforms, pro‐inflammatory cytokines, receptor for advanced glycation end products (RAGE) and fatty acid metabolism were evaluated through Western blotting. The mitochondrial oxygen consumption rate and adenosine triphosphate (ATP) production were investigated using Seahorse XF24 extracellular flux analyzer and bioluminescence assay. Fluorescence intensity using 2′, 7′‐dichlorodihydrofluorescein diacetate was used to evaluate mitochondrial oxidative stress. NaHS attenuated the impaired basal and maximal respiration, ATP production and ATP synthesis and enhanced mitochondrial oxidative stress in TNF‐α‐treated HL‐1 cells. TNF‐α‐treated HL‐1 cells exhibited lower expression of PPAR‐α, PPAR‐δ, phosphorylated 5′ adenosine monophosphate‐activated protein kinase‐α2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase‐1, PPAR‐γ coactivator 1‐α and diacylglycerol acyltransferase 1 protein, but higher expression of PPAR‐γ, interleukin‐6 and RAGE protein than control or combined NaHS and TNF‐α‐treated HL‐1 cells. NaHS modulates the effects of TNF‐α on mitochondria and the cardiometabolic system, suggesting its therapeutic potential for inflammation‐induced cardiac dysfunction.

Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress

“…It is worth noting that even in myocardium with impaired glucose metabolism, oxidative stress and related structural remodelling are the basis of abnormal electrical activity. H 2 S improves mitochondrial oxidative stress, respiratory dysfunction, and reduces apoptosis in HL-1 cells caused by glucose metabolism disorder, and in turn can improve atrial function in mice ( Garcia et al, 2017 ; Lee et al, 2019 ). This has similar effects to reducing oxidative stress to inhibit HL-1 cell apoptosis and improve left atrial structural remodelling induced by AF in mice ( Johnston et al, 1990 ).…”

“…Ang II + NaHS group: HL-1 cells were pre-incubated with NaHS (100 μM) for 24 h, and then treated with Ang-II for another 24 h ( Lee et al, 2019 ).…”

Carnitine Palmitoyltransferase System: A New Target for Anti-Inflammatory and Anticancer Therapy?

“…In TNFα-stimulated mouse cardiac muscle cells, sodium hydrosulfide ameliorated the impaired mitochondrial respiration and ATP production/synthesis, and attenuated excess oxidative stress, which might be due to the enhanced expression of metabolic indices such as CPT1. The study indicated the therapeutic potential of sodium hydrosulfide for inflammation-associated cardiac dysfunctions ( Lee et al, 2019 ).…”

Inflammation and mitochondria in the pathogenesis of chronic Chagas disease cardiomyopathy

“…72 The authors showed that activation of AMPK can mediate the transport of fatty acids into mitochondria through phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), an important enzyme that inhibits the fatty acid oxidation, AMPK therefore enhanced the oxidation of fatty acids in HL-1 cardiomyocyte cells. 73 The same group reported that the expression of PPAR-α and PPAR-δ, transcription factors that regulate fatty acid oxidation, is decreased when cells are exposed to TNF-α. 73 TNF-α decreased carnitine O-palmitoyltransferase 1 (CPT-1) expression, which is required for the translocation of long-chain fatty acids into the mitochondrial matrix (a limiting step in beta-oxidation).…”