Heart and kidney H2S production is reduced in hypertensive and older rats

Szlęzak, Dominika; Hutsch, Tomasz; Ufnal, Marcin; Wróbel, Maria

doi:10.1016/j.biochi.2022.04.013

Cited by 11 publications

(7 citation statements)

References 58 publications

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“…In recent years, our research investigations have focused on the presence and role of enzymes (MPST, CTH, CBS) involved in the metabolism of low-molecular-weight sulfur compounds and H 2 S in normal [31,32] and/or cancer cells [33,34]. Our other studies on in vivo animal model confirmed the significant role of MPST and CTH in the production of hydrogen sulfide in the heart and kidneys, respectively [35]. Enzymes containing cysteine residues in the active site play a crucial role in biological processes, such as the regulation of cell cycle progression, apoptosis or signal transduction [36].…”

Section: Discussionsupporting

confidence: 52%

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

Bentke-Imiolek,

Szlęzak,

Zarzycka

et al. 2024

Biomolecules

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S-allyl-L-cysteine (SAC) is a sulfur compound present in fresh garlic. The reference literature describes its anticancer, antioxidant and neuroprotective effects. Breast cancer is infamously known as one of the most commonly diagnosed malignancies among women worldwide. Its morbidity and mortality make it reasonable to complete and expand knowledge on this cancer’s characteristics. Hydrogen sulfide (H2S) and its naturally occurring donors are well-known investigation subjects for diverse therapeutic purposes. This study was conducted to investigate the SAC antiproliferative potential and effect on three enzymes involved in H2S metabolism: 3-mercaptopyruvate sulfurtransferase (MPST), cystathionine γ-lyase (CTH), and cystathionine β-synthase (CBS). We chose the in vitro cellular model of human breast adenocarcinomas: MCF-7 and MDA-MB-231. The expression of enzymes after 2, 4, 6, 8, and 24 h incubation with 2.24 mM, 3.37 mM, and 4.50 mM SAC concentrations was examined. The number of living cells was determined by the MTS assay. Changes in cellular plasma membrane integrity were measured by the LDH test. Expression changes at the protein level were analyzed using Western blot. A significant decrease in viable cells was registered for MCF-7 cells after all incubation times upon 4.50 mM SAC exposure, and after 6 and 24 h only in MDA-MB-231 upon 4.50 mM SAC. In both cell lines, the MPST gene expression significantly increased after the 24 h incubation with 4.50 mM SAC. S-allyl-L-cysteine had opposite effects on changes in CTH and CBS expression in both cell lines. In our research model, we confirmed the antiproliferative potential of SAC and concluded that our studies provided current information about the increase in MPST gene expression mediated by S-allyl-L-cysteine in the adenocarcinoma in vitro cellular model for the MCF-7 and MDA-MB-231 cell lines. Further investigation of this in vitro model can bring useful information regarding sulfur enzyme metabolism of breast adenocarcinoma and regulating its activity and expression (gene silencing) in anticancer therapy.

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Section: Discussionsupporting

confidence: 52%

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

Bentke-Imiolek,

Szlęzak,

Zarzycka

et al. 2024

Biomolecules

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“…For example, nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a redox-responsive factor and mediates ROS elimination, 256 while downregulation of NRF2 is observed in elderly individuals. As expected, reduced ROS production or the oxidized form of glutathione (GSSG) disposition ameliorates cardiac aging, 257,258 supporting the concept that ROS derived by mitochondria are harmful to aging hearts. Recently, the correlation between ROS with cardiac aging is reported in some preclinical studies.…”

Section: Mitochondrial Ros and Mtdnamentioning

confidence: 54%

Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications

Xie

Deng

et al. 2023

Sig Transduct Target Ther

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Cardiac aging is evident by a reduction in function which subsequently contributes to heart failure. The metabolic microenvironment has been identified as a hallmark of malignancy, but recent studies have shed light on its role in cardiovascular diseases (CVDs). Various metabolic pathways in cardiomyocytes and noncardiomyocytes determine cellular senescence in the aging heart. Metabolic alteration is a common process throughout cardiac degeneration. Importantly, the involvement of cellular senescence in cardiac injuries, including heart failure and myocardial ischemia and infarction, has been reported. However, metabolic complexity among human aging hearts hinders the development of strategies that targets metabolic susceptibility. Advances over the past decade have linked cellular senescence and function with their metabolic reprogramming pathway in cardiac aging, including autophagy, oxidative stress, epigenetic modifications, chronic inflammation, and myocyte systolic phenotype regulation. In addition, metabolic status is involved in crucial aspects of myocardial biology, from fibrosis to hypertrophy and chronic inflammation. However, further elucidation of the metabolism involvement in cardiac degeneration is still needed. Thus, deciphering the mechanisms underlying how metabolic reprogramming impacts cardiac aging is thought to contribute to the novel interventions to protect or even restore cardiac function in aging hearts. Here, we summarize emerging concepts about metabolic landscapes of cardiac aging, with specific focuses on why metabolic profile alters during cardiac degeneration and how we could utilize the current knowledge to improve the management of cardiac aging.

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“…Because different H 2 S-producing enzymes can have different biological roles, most relevant for our study are the changes in the 3-MST pathway associated with aging (and with obesity). 3-MST expression shows an age-dependent decrease in the heart and kidney of rats and mice [ 48 – 50 ]. Moreover, the bioenergetic stimulatory effect of 3-mercaptopyruvate (the substrate of 3-MST) was markedly lower in liver mitochondria isolated from aged mice, when compared to the marked stimulating effect seen in mitochondria isolated from young mice [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

et al. 2022

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H2S is generated in the adipose tissue by cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S plays multiple roles in the regulation of various metabolic processes, including insulin resistance. H2S biosynthesis also occurs in adipocytes. Aging is known to be associated with a decline in H2S. Therefore, the question arises whether endogenous H2S deficiency may affect the process of adipocyte maturation and lipid accumulation. Among the three H2S-generating enzymes, the role of 3-MST is the least understood in adipocytes. Here we tested the effect of the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) and the H2S donor (GYY4137) on the differentiation and adipogenesis of the adipocyte-like cells 3T3-L1 in vitro. 3T3-L1 cells were differentiated into mature adipocytes in the presence of GYY4137 or HMPSNE. HMPSNE significantly enhanced lipid accumulation into the maturing adipocytes. On the other hand, suppressed lipid accumulation was observed in cells treated with the H2S donor. 3-MST inhibition increased, while H2S donation suppressed the expression of various H2S-producing enzymes during adipocyte differentiation. 3-MST knockdown also facilitated adipocytic differentiation and lipid uptake. The underlying mechanisms may involve impairment of oxidative phosphorylation and fatty acid oxidation as well as the activation of various differentiation-associated transcription factors. Thus, the 3-MST/H2S system plays a tonic role in suppressing lipid accumulation and limiting the differentiation of adipocytes. Stimulation of 3-MST activity or supplementation of H2S—which has been recently linked to various experimental therapeutic approaches during aging—may be a potential experimental approach to counteract adipogenesis.

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Heart and kidney H2S production is reduced in hypertensive and older rats

Cited by 11 publications

References 58 publications

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

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