Exploring mitochondrial hydrogen sulfide signalling for therapeutic interventions in vascular diseases

Sanchez, Lorena Diaz; Sanchez-Aranguren, Lissette; Marwah, Mandeep; Wang, Keqing; Spickett, Corinne M.; Griffiths, Helen R.; Dias, Irundika H.K.

doi:10.1016/j.arres.2022.100030

Cited by 6 publications

(11 citation statements)

References 156 publications

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“…However, CBS and CSE can also translocate into the mitochondria when the activity of 3MST is suppressed under challenging conditions, such as hypoxia, to promote the mitochondrial generation of H 2 S [ 5 , 34 ]. The endogenous H 2 S is generally maintained at a low steady-state level to elicit various physiological effects and maintain multiple cellular functions [ 35 ], whose decline has been demonstrated to associate to aging and many age-related diseases. It was reported that H 2 S levels in the heart, liver, and kidney tissues were significantly decreased in senescent mice [ 36 ].…”

Section: Antioxidant Activities: a Conventional Anti-aging Paradigm O...mentioning

confidence: 99%

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

Huynh

Wang

et al. 2022

Antioxidants

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The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.

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Section: Antioxidant Activities: a Conventional Anti-aging Paradigm O...mentioning

confidence: 99%

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

Huynh

Wang

et al. 2022

Antioxidants

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“…In mammalian systems, H 2 S is synthesised by the transsulfuration pathway and mitochondrial cysteine catabolism pathway. In this regard, mitochondria play an important role in H 2 S metabolism via the mitochondrial sulfide oxidation pathway [ 15 ]. As a gaseous molecule, H 2 S can easily travel across membranes.…”

Section: Introductionmentioning

confidence: 99%

“…H 2 S entering mitochondria is oxidised by the inter-mitochondrial membrane protein, sulfide quinone oxidoreductase (SQR), to generate persulfides that are later oxidised to short-lived sulfite (SO 3 2− ), thiosulfate (S 2 O 3 2− ) and sulfate (SO 4 2− ) [ 15 ]. H 2 S is considered a toxic molecule at high concentrations as these oxidation products cause cytotoxic effects by altering mitochondrial membrane potential and disrupting cellular energy production [ 15 ]. Therefore, the therapeutic potential of H 2 S should be explored at a sub-toxic dose.…”

Section: Introductionmentioning

confidence: 99%

TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide

et al. 2023

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Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H2S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H2S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H2S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H2S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H2S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-α increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-α also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H2S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-α alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-α exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H2S via the mitochondrial-driven pathway.

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“…Hydrogen sulphide (H 2 S) is a gaseous molecule with the characteristic foul odour of rotten eggs that was previously considered to be poisonous [ 6 ]. However, research has demonstrated that mammalian cells produce low levels of H 2 S as an important signalling molecule [ 7 , 8 , 9 ]. It has multiple effects in many body organ systems including the central and peripheral nervous systems, cardiovascular, gastrointestinal and respiratory systems [ 6 ] with the ability to regulate cellular metabolism [ 9 , 10 ], angiogenesis [ 11 ], inflammatory responses [ 12 ] and oxidative stress [ 13 ] through several mechanisms including the preservation of the mitochondrial metabolic and cellular functions [ 9 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, research has demonstrated that mammalian cells produce low levels of H 2 S as an important signalling molecule [ 7 , 8 , 9 ]. It has multiple effects in many body organ systems including the central and peripheral nervous systems, cardiovascular, gastrointestinal and respiratory systems [ 6 ] with the ability to regulate cellular metabolism [ 9 , 10 ], angiogenesis [ 11 ], inflammatory responses [ 12 ] and oxidative stress [ 13 ] through several mechanisms including the preservation of the mitochondrial metabolic and cellular functions [ 9 , 14 ]. Exogenous H 2 S has been shown to be cardioprotective in various experimental models of cardiac injury [ 15 , 16 ], offering a potential therapeutic option where a lack of its endogenous availability has resulted in myocardial ischemia and reperfusion injuries [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Sodium Thiosulphate-Loaded Liposomes Control Hydrogen Sulphide Release and Retain Its Biological Properties in Hypoxia-like Environment

et al. 2022

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Hypoxia, or insufficient oxygen availability is a common feature in the development of a myriad of cardiovascular-related conditions including ischemic disease. Hydrogen sulphide (H2S) donors, such as sodium thiosulphate (STS), are known for their cardioprotective properties. However, H2S due to its gaseous nature, is released and cleared rapidly, limiting its potential translation to clinical settings. For the first time, we developed and characterised liposome formulations encapsulating STS and explored their potential for modulating STS uptake, H2S release and the ability to retain pro-angiogenic and biological signals in a hypoxia-like environment mirroring oxygen insufficiency in vitro. Liposomes were prepared by varying lipid ratios and characterised for size, polydispersity and charge. STS liposomal encapsulation was confirmed by HPLC-UV detection and STS uptake and H2S release was assessed in vitro. To mimic hypoxia, cobalt chloride (CoCl2) was administered in conjunction with formulated and non-formulated STS, to explore pro-angiogenic and metabolic signals. Optimised liposomal formulation observed a liposome diameter of 146.42 ± 7.34 nm, a polydispersity of 0.22 ± 0.19, and charge of 3.02 ± 1.44 mV, resulting in 25% STS encapsulation. Maximum STS uptake (76.96 ± 3.08%) from liposome encapsulated STS was determined at 24 h. Co-exposure with CoCl2 and liposome encapsulated STS resulted in increased vascular endothelial growth factor mRNA as well as protein expression, enhanced wound closure and increased capillary-like formation. Finally, liposomal STS reversed metabolic switch induced by hypoxia by enhancing mitochondrial bioenergetics. These novel findings provide evidence of a feasible controlled-delivery system for STS, thus H2S, using liposome-based nanoparticles. Likewise, data suggests that in scenarios of hypoxia, liposomal STS is a good therapeutic candidate to sustain pro-angiogenic signals and retain metabolic functions that might be impaired by limited oxygen and nutrient availability.

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Exploring mitochondrial hydrogen sulfide signalling for therapeutic interventions in vascular diseases

Cited by 6 publications

References 156 publications

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide

Sodium Thiosulphate-Loaded Liposomes Control Hydrogen Sulphide Release and Retain Its Biological Properties in Hypoxia-like Environment

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