The polysulfide diallyl trisulfide protects the ischemic myocardium by preservation of endogenous hydrogen sulfide and increasing nitric oxide bioavailability

Predmore, Benjamin L.; Kondo, Kazuhisa; Bhushan, Shashi; Zlatopolsky, Maxim; King, Adrienne L.; Aragón, Juan Pablo; Grinsfelder, D. Bennett; Condit, Marah E.; Lefer, David J.

doi:10.1152/ajpheart.00044.2012

Cited by 164 publications

(138 citation statements)

References 28 publications

(36 reference statements)

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“…Although originally considered separate signaling pathways, recent evidence suggests cross-talk between H 2 S and NO signaling in the cardiovascular system. Previous studies have reported that vascular function, inflammation, angiogenesis, and ischemic injury are regulated by cross-talk between the H 2 S and NO signaling pathways (8,(19)(20)(21). We postulate that the cross-talk between H 2 S and NO is mediated via the phosphorylation of eNOS (enzymatic production of NO).…”

Section: Discussionmentioning

confidence: 80%

“…Exogenous H 2 S therapy has been demonstrated to attenuate myocardial I/R injury in mice (7,8,12). To determine whether the protective mechanism is dependent on eNOS, we first used a mouse model with global genetic ablation of eNOS.…”

Section: H 2 S Therapy Restores Enos Function and No Bioavailability mentioning

confidence: 99%

“…The biological profiles of H 2 S and NO are similar, and both molecules are known to protect cells against various injurious states that result in organ injury. Although H 2 S and NO are thought to modulate independent signaling pathways, there is limited evidence of cross-talk between these two molecules (5, 6).H 2 S therapeutics and endogenous overexpression of CSE have been shown to attenuate ischemia/reperfusion (I/R) injury (7,8). Similarly, NO therapy and eNOS gene overexpression are also protective in ischemic disease states (9).…”

mentioning

confidence: 99%

“…H 2 S therapeutics and endogenous overexpression of CSE have been shown to attenuate ischemia/reperfusion (I/R) injury (7,8). Similarly, NO therapy and eNOS gene overexpression are also protective in ischemic disease states (9).…”

mentioning

confidence: 99%

“…Similarly, NO therapy and eNOS gene overexpression are also protective in ischemic disease states (9). Given the potent antioxidant actions of H 2 S (10, 11) and the effects of exogenous H 2 S therapy on NO bioavailability (5,8), we investigated the effects of genetic deletion of the cystathionase gene (Cth, i.e., CSE KO) on the regulation of eNOS function and NO bioavailability.…”

mentioning

confidence: 99%

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Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

King

Polhemus

Bhushan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Previous studies have demonstrated that hydrogen sulfide (H 2 S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H 2 S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H 2 S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H 2 S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H 2 S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H 2 S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H 2 S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.eNOS uncoupling | myocardial infarction | cystathionase | Cth | nitrite H ydrogen sulfide (H 2 S), historically known for its odorous smell and toxicity at high concentrations, has recently been classified as a physiological signaling molecule with robust cytoprotective actions in multiple organ systems (1-3). H 2 S is produced enzymatically in mammalian tissues by three different enzymes: cystathionine γ-lyase (CSE), cystathionine beta-synthase (CBS), and 3-mercatopyruvate sulfurtransferase (3-MST). CSE, involved in the cysteine biosynthesis pathway, coordinates with L-cystine to produce H 2 S within the vasculature and is known to regulate blood pressure, modulate cellular metabolism, promote angiogenesis, regulate ion channels, and mitigate fibrosis and inflammation (4). Endothelial nitric oxide synthase (eNOS) catalyzes the production of nitric oxide (NO) from L-arginine within the endothelium to regulate vascular tone via cGMP signaling in vascular smooth muscle, mitochondrial respiration, platelet function, inflammation, and angiogenesis. The biological profiles of H 2 S and NO are similar, and both molecules are known to protect cells against various injurious states that result in organ injury. Although H 2 S and NO are thought to modulate independent signaling pathways, there is limited evidence of cross-talk between these two molecules (5, 6).H 2 S therapeutics and endogenous overexpression of CSE have been shown to attenuate ischemia/reperfusion (I/R) injury (7,8). Similarly, NO therapy and eNOS gene overexpression are also protective in ischemic disease states (9). Given the potent antioxidant actions of H 2 S (10, 11) and the effects of exogenous H 2 S therapy on NO bioavailability (5, 8), we investigated the effects of genetic deletion of the cystathionase gene (Cth, i.e., CSE KO) on the regulation of eNOS function and NO bioavailability. ResultsSulfide Levels are Reduced in CSE KO Mice. Whole blood and heart specimens were collected from WT and CSE KO mice to measure H 2 S levels using a high-sensitivity gas chromato...

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Section: Discussionmentioning

confidence: 80%

Section: H 2 S Therapy Restores Enos Function and No Bioavailability mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

King

Polhemus

Bhushan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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315

312

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Hydrogen Sulfide: An Emerging Precision Strategy for Gas Therapy

Ding

Chang

et al. 2021

Adv Healthcare Materials

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Advances in nanotechnology have enabled the rapid development of stimuli-responsive therapeutic nanomaterials for precision gas therapy. Hydrogen sulfide (H 2 S) is a significant gaseous signaling molecule with intrinsic biochemical properties, which exerts its various physiological effects under both normal and pathological conditions. Various nanomaterials with H 2 S-responsive properties, as new-generation therapeutic agents, are explored to guide therapeutic behaviors in biological milieu. The cross disciplinary of H 2 S is an emerging scientific hotspot that studies the chemical properties, biological mechanisms, and therapeutic effects of H 2 S. This review summarizes the state-of-art research on H 2 S-related nanomedicines. In particular, recent advances in H 2 S therapeutics for cancer, such as H 2 S-mediated gas therapy and H 2 S-related synergistic therapies (combined with chemotherapy, photodynamic therapy, photothermal therapy, and chemodynamic therapy) are highlighted. Versatile imaging techniques for real-time monitoring H 2 S during biological diagnosis are reviewed. Finally, the biosafety issues, current challenges, and potential possibilities in the evolution of H 2 S-based therapy that facilitate clinical translation to patients are discussed.

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Manganese Porphyrin‐Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from a Hydrogen Sulfide Donor

Young,

Yamane,

GharehTapeh

et al. 2023

Adv Healthcare Materials

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Per/polysulfide species that are generated from endogenously produced hydrogen sulfide have critical regulatory roles in a wide range of cellular processes. However, the lack of delivery systems that enable controlled and sustained release of these unstable species in biological systems hinders the advancement of sulfide biology research, as well as the translation of knowledge to therapeutic applications. Here, a novel approach is developed to generate per/polysulfide species in cells by combining an H2S donor and manganese porphyrin‐containing polymeric micelles (MnPMCs) that catalyze oxidization of H2S to per/polysulfide species. MnPMCs serve as a catalyst for H2S oxidation in aerobic phosphate buffer. HPLC‐MS/MS analysis reveals that H2S oxidation by MnPMCs in the presence of glutathione results in the formation of glutathione‐SnH (n = 2 and 3). Furthermore, co‐treatment of human umbilical vein endothelial cells with the H2S donor anethole dithiolethione and MnPMCs increases intracellular per/polysulfide levels and induces a proangiogenic response. Co‐delivery of MnPMCs and an H2S donor is a promising approach for controlled delivery of polysulfides for therapeutic applications.

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The polysulfide diallyl trisulfide protects the ischemic myocardium by preservation of endogenous hydrogen sulfide and increasing nitric oxide bioavailability

Cited by 164 publications

References 28 publications

Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

Hydrogen Sulfide: An Emerging Precision Strategy for Gas Therapy

Manganese Porphyrin‐Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from a Hydrogen Sulfide Donor

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