Hydrogen Sulfide Protects the Retina from Light-induced Degeneration by the Modulation of Ca2+ Influx

Mikami, Yuzuru; Shibuya, Norihiro; Kimura, Yoshinobu; Nagahara, Noriyuki; Yamada, Masahiro; Kimura, Hideo

doi:10.1074/jbc.m111.298208

Cited by 135 publications

(161 citation statements)

References 48 publications

(38 reference statements)

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“…These oxidants cause the oxidative modification of proteins and lipids seen in vivo in patients with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. H 2 S also protects retinal neurons from light-induced degeneration by suppressing the excessive Ca 2 + influx (43). The cytoprotective effect was also found by David Lefer and colleagues in the cardiovascular system.…”

Section: Introductionmentioning

confidence: 56%

“…CBS and CSE are localized to the cytoplasm, while 3MST is mainly localized to the mitochondrial matrix, with a pH of approximately 8 (45). 3MST is localized to neurons in the brain and retina (43,58). Neither CBS nor CSE was found in the retina.…”

Section: Mst With Catmentioning

confidence: 98%

“…The activity of CBS is enhanced by S-adenosyl methionine, and that of 3MST pathway is regulated by Ca 2 + (1,43). Cystathionine c-lyase (CSE) is expressed little in the brain (1,26).…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Kimura

Shibuya²,

Kimura³

2012

Antioxidants & Redox Signaling

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256

190

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Significance: Accumulating evidence shows that hydrogen sulfide may function as a signaling molecule in processes such as neuromodulation in the brain and smooth muscle relaxation in the vascular system. It also has a cytoprotective effect, since it can protect neurons and cardiac muscle from oxidative stress and ischemiareperfusion injury, respectively. Hydrogen sulfide can also modulate inflammation, insulin release, and angiogenesis. Recent Advances: The regulation of the activity of 3-mercaptopyruvate sulfur transferase (3MST) along with cysteine aminotransferase (CAT), one of the H 2 S producing pathways, has been demonstrated. The production of H 2 S by the pathway, which is regulated by Ca 2+ and facilitated by thioredoxin and dihydrolipoic acid, is also involved in H 2 S signaling as well as cytoprotection. Sulfur hydration of proteins by H 2 S has been proposed to modulate protein functions. H 2 S-sensitive fluorescent probes, which enable us to measure the localization of H 2 S in real time, have been developed. Critical Issues: The basal concentrations of H 2 S have recently been measured and found to be much lower than those initially reported. However, the concentration of H 2 S reached in stimulated cells, as well as the regulation of H 2 S producing enzymes is not well understood. It has been proposed that some of the effects of H 2 S on the regulation of enzymes and receptors might be explained through the properties of sulfane sulfur (S 0 ), another form of active sulfur. Future Directions: The determination of H 2 S concentrations in activated cells using new methods including H 2 S-sensitive fluorescent probes, as well as the investigation of the effects of H 2 S using specific inhibitors, may provide better understanding of the physiological function of this molecule. Clarifying mechanisms of H 2 S activity may also facilitate the development of new therapeutic compounds. Antioxid. Redox Signal. 17, 45-57.

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Section: Introductionmentioning

confidence: 56%

Section: Mst With Catmentioning

confidence: 98%

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Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Kimura

Shibuya²,

Kimura³

2012

Antioxidants & Redox Signaling

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256

190

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“…S-adenosylmethionine allosterically activates CBS (152) and although CBS contains a heme group that can be inhibited by CO, neither nitric oxide (NO) nor O 2 appears effective at physiological concentrations (4). CSE and both cytosolic and mitochondrial CAT activity are inhibited by calcium, independent of calmodulin (104,105).…”

Section: Metabolic Relationships Between H 2 S and Omentioning

confidence: 99%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

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Significance: Although oxygen (O 2 )-sensing cells and tissues have been known for decades, the identity of the O 2 -sensing mechanism has remained elusive. Evidence is accumulating that O 2 -dependent metabolism of hydrogen sulfide (H 2 S) is this enigmatic O 2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H 2 S synthesis and metabolism have shown that reciprocal H 2 S/O 2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O 2 controls H 2 S inactivation, and the effects of H 2 S on downstream signaling events are consistent with those activated by hypoxia. H 2 S-mediated O 2 sensing has been demonstrated in a variety of O 2 -sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H 2 S and its metabolites. Future Directions: Development of specific inhibitors of H 2 S metabolism and effector activation as well as cellular organelle-targeted compounds that release H 2 S in a timeor environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377-397.

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“…Despite the fact that H 2 S is recognized to be neuroprotective [12,13] and serves as a protective mediator for various tissues [14][15][16], the similar function of bound sulfur is not well known. Therefore, further study is required to resolve the individual mechanisms by which H 2 S and bound sulfur may perform physiological roles.…”

Section: Introductionmentioning

confidence: 99%

Polysulfide exerts a protective effect against cytotoxicity caused by t‐buthylhydroperoxide through Nrf2 signaling in neuroblastoma cells

et al. 2013

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a b s t r a c tPolysulfide is a bound sulfur species derived from endogenous H 2 S. When mouse neuroblastoma, Neuro2A cells were exposed to tert-butyl hydroperoxide after treatment with polysulfide, a significant decline in cell toxicity was observed. Rapid uptake of polysulfides induced translocation of Nrf2 into the nucleus, resulting in acceleration of GSH synthesis and HO-1 expression. We demonstrated that polysulfide reversibly modified Keap1 to form oxidized dimers and induced the translocation of Nrf2. Moreover, polysulfide treatment accelerated Akt phosphorylation, which is a known pathway of Nrf2 phosphorylation. Thus, polysulfide may mediate the activation of Nrf2 signaling, thereby exerting protective effects against oxidative damage in Neuro2A cells.

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Hydrogen Sulfide Protects the Retina from Light-induced Degeneration by the Modulation of Ca2+ Influx

Cited by 135 publications

References 48 publications

Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Hydrogen Sulfide Is a Signaling Molecule and a Cytoprotectant

Hydrogen sulfide as an oxygen sensor

Polysulfide exerts a protective effect against cytotoxicity caused by t‐buthylhydroperoxide through Nrf2 signaling in neuroblastoma cells

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