Hydrogen sulfide attenuates calcification of vascular smooth muscle cells via KEAP1/NRF2/NQO1 activation

Aghagolzadeh, Parisa; Radpour, Ramin; Bachtler, Matthias; Goor, Harry van; Smith, Edward; Lister, Adam; Odermatt, Alex; Feelisch, Martin; Pasch, Andreas

doi:10.1016/j.atherosclerosis.2017.08.012

Cited by 89 publications

(84 citation statements)

References 47 publications

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“…In vivo and in vitro evidence has shown that oxidation and oxidation products are widely present in degenerated intervertebral discs . Studies have reported that oxidative stress may increase the incidence of apoptosis through the mitochondria‐dependent pathway in various cell types; in addition, reactive oxygen species and oxidative stress products have been shown to increase ectopic calcification formation in cardiovascular cells . Han et al reported that oxidative stress may induce apoptosis and promote calcification in disc cartilage endplate cells .…”

Section: Discussionmentioning

confidence: 99%

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Zhang

Lin

Tian

et al. 2018

J Cellular Molecular Medi

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Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose‐dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3‐methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX‐527 suppressed melatonin‐induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1‐autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1‐autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.

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Section: Discussionmentioning

confidence: 99%

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Zhang

Lin

Tian

et al. 2018

J Cellular Molecular Medi

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“…A well known therapeutic attribute of MnPs is their ability to protect healthy cells and increase susceptibility of malignant cells to radiation therapy. This process has been attributed in part to increased H 2 O 2 which, in a process catalyzed by MnP, oxidizes signaling proteins such as NFκB [4,10,31]. Our results suggest that persulfides produced by MnP oxidation of H 2 S could have a similar effect with the added bonus of direct oxidant scavenging by persulfides.…”

Section: Antioxidant Function Of Mnp-generated Polysulfidesmentioning

confidence: 64%

Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

et al. 2020

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Manganese porphyrins (MnPs), MnTE-2-PyP5+, MnTnHex-2-PyP5+ and MnTnBuOE-2-PyP5+, are superoxide dismutase (SOD) mimetics and form a redox cycle between O2 and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (H2O2). We previously found that MnPs oxidize hydrogen sulfide (H2S) to polysulfides (PS; H2Sn, n = 2–6) in buffer. Here, we examine the effects of MnPs for 24 h on H2S metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using H2S (AzMC, MeRho-AZ) and PS (SSP4) fluorophores. All MnPs decreased intracellular H2S production and increased intracellular PS. H2S metabolism and PS production were unaffected by cellular O2 (5% versus 21% O2), H2O2 or ascorbic acid. We observed with confocal microscopy that mitochondria are a major site of H2S production in HEK293 cells and that MnPs decrease mitochondrial H2S production and increase PS in what appeared to be nucleoli and cytosolic fibrillary elements. This supports a role for MnPs in the metabolism of H2S to PS, the latter serving as both short- and long-term antioxidants, and suggests that some of the biological effects of MnPs may be attributable to sulfur metabolism.

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“…CPP2-induced calcification of VSMCs was largely ameliorated by the H 2 S-donor NaHS via activation of the KEAP1/NRF2/NQO1 pathway (Aghagolzadeh et al, 2017).…”

Section: H 2 S In Vascular Calcificationmentioning

confidence: 96%

The role of the gasotransmitter hydrogen sulfide in pathological calcification

Castelblanco

Nasi

et al. 2019

British J Pharmacology

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Calcification is the deposition of minerals, mainly hydroxyapatite, inside the cell or in the extracellular matrix. Physiological calcification is central for many aspects of development including skeletal and tooth growth; conversely, pathological mineralization occurs in soft tissues and is significantly associated with malfunction and impairment of the tissue where it is located. Various mechanisms have been proposed to explain calcification. However, this research area lacks a more integrative, systemic, and global perspective that could explain both physiological and pathological processes. In this review, we propose such an integrated explanation. Hydrogen sulfide (H2S) is a newly recognized multifunctional gasotransmitters and tis actions have been studied in different physiological and pathological contexts, but little is known about its potential role on calcification. Interestingly, we found that H2S promotes calcification under physiological conditions and has an inhibitory effect on pathological processes. This makes H2S a potential therapy for diseases related to pathological calcification. Linked Articles This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc

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Hydrogen sulfide attenuates calcification of vascular smooth muscle cells via KEAP1/NRF2/NQO1 activation

Abstract: Sulfide attenuates CPP-induced VSMC calcification in vitro via the KEAP1-NRF2 redox sensing/stress response system by enhancing NQO1 expression.

Cited by 89 publications

References 47 publications

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

The role of the gasotransmitter hydrogen sulfide in pathological calcification

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