N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production

Ezeriņa, Daria; Takano, Yoko; Hanaoka, Kenjiro; Urano, Yasuteru; Dick, Tobias P.

doi:10.1016/j.chembiol.2018.01.011

Cited by 300 publications

(258 citation statements)

References 66 publications

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“…To examine the role of oxidative stress in high glucose-induced cardiac fibroblast activation, we treated cardiac fibroblasts with the antioxidant NAC. NAC is a thiol-containing radical scavenger and glutathione precursor [26,27]. Similarly, antioxidant treatment using NAC also attenuated high glucose-induced increases in ROS production, fibroblast proliferation and collagen synthesis in cultured cardiac fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts

Tsai

Loh

Lee

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diabetes is associated with increased incidence of myocardial dysfunction, which is partly characterized by interstitial and perivascular fibrosis. Cardiac fibroblasts have been identified as an important participant in the development of cardiac fibrosis. Exposure of cultured cardiac fibroblasts to high glucose resulted in increased collagen synthesis. Tanshinone IIA can alleviate the ventricular fibrosis that develops in a number of different experimental conditions. However, whether tanshinone IIA can prevent high glucose-induced collagen synthesis in cardiac fibroblasts remains unknown. The aim of this study was to evaluate the effects of tanshinone IIA on high glucose-induced collagen synthesis in cardiac fibroblasts. Methods: Rat cardiac fibroblasts were cultured in high glucose (25 mM) media in the absence or presence of tanshinone IIA and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production and related signaling molecules were assessed by ³H-proline incorporation, quantitative polymerase chain reaction, enzyme linked immunosorbent assay, and Western blotting. Results: The results indicate cardiac fibroblasts exposed to high glucose condition show increased cell proliferation and collagen synthesis and these effects were abolished by tanshinone IIA treatment. Furthermore, the inhibitory effect of tanshinone IIA on high glucose induced cell proliferation and collagen synthesis may be associated with its activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of TGF-β1 production and Smad2/3 phosphorylation. Conclusion: In summary, our results highlights the critical role tanshinone IIA plays as an antioxidant in attenuating high glucose-mediated collagen synthesis through inhibiting TGF-β1/Smad signaling in cardiac fibroblasts which provide a mechanistic basis for the clinical application of tanshinone IIA in the treating diabetic-related cardiac fibrosis.

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Section: Discussionmentioning

confidence: 99%

Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts

Tsai

Loh

Lee

et al. 2018

Cell Physiol Biochem

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“…This targeted depletion of H 2 O 2 was recapitulated by the antioxidants N-acetylcysteine (NAC) and the mitochondrial •O 2 − scavenger MitoTempo (Fig. S5 C), which have both been shown to scavenge mitochondrial ROS (Nazarewicz et al, 2013; Ezerina et al, 2018). In contrast, supplementation with untargeted exogenous catalase failed to rescue the effects of NNT knockdown on ACO2 activity, highlighting the need for targeted expression (Fig.…”

Section: Resultsmentioning

confidence: 94%

Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function

Ward

Kang

Falzone

et al. 2020

Journal of Experimental Medicine

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Human lung tumors exhibit robust and complex mitochondrial metabolism, likely precipitated by the highly oxygenated nature of pulmonary tissue. As ROS generation is a byproduct of this metabolism, reducing power in the form of nicotinamide adenine dinucleotide phosphate (NADPH) is required to mitigate oxidative stress in response to this heightened mitochondrial activity. Nicotinamide nucleotide transhydrogenase (NNT) is known to sustain mitochondrial antioxidant capacity through the generation of NADPH; however, its function in non-small cell lung cancer (NSCLC) has not been established. We found that NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression. We further show that NNT loss elicits mitochondrial dysfunction independent of substantial increases in oxidative stress, but rather marked by the diminished activities of proteins dependent on resident iron-sulfur clusters. These defects were associated with both NADPH availability and ROS accumulation, suggesting that NNT serves a specific role in mitigating the oxidation of these critical protein cofactors.

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“…In the absence of a known sulfur acceptor(s) for STR18, we have investigated the capability of STR18 to transfer a sulfur atom to a protein substrate by using roGFP2 which was previously used to monitor persulfide generation in living cells (33). We have thus tested the oxidation of a pre-reduced roGFP2 in the presence of STR18 and thiosulfate ( Fig.…”

Section: Str18 Promotes Trans-persulfidation Reaction Between Two Promentioning

confidence: 99%

The cytosolicArabidopsis thalianacysteine desulfurase ABA3 delivers sulfur to the sulfurtransferase STR18

Selles

Dhalleine

Hériché

et al. 2020

Preprint

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N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production

Cited by 300 publications

References 66 publications

Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts

Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts

Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function

The cytosolicArabidopsis thalianacysteine desulfurase ABA3 delivers sulfur to the sulfurtransferase STR18

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