» Articles » PMID: 29926377

Role of Nitric Oxide and Hydrogen Sulfide in Ischemic Stroke and the Emergent Epigenetic Underpinnings

Overview
Journal Mol Neurobiol
Date 2018 Jun 22
PMID 29926377
Citations 28
Authors
Affiliations
Soon will be listed here.
Abstract

Nitric oxide (NO) and hydrogen sulfide (HS) are the key gasotransmitters with an imperious role in the maintenance of cerebrovascular homeostasis. A decline in their levels contributes to endothelial dysfunction that portends ischemic stroke (IS) or cerebral ischemia/reperfusion (CI/R). Nevertheless, their exorbitant production during CI/R is associated with exacerbation of cerebrovascular injury in the post-stroke epoch. NO-producing nitric oxide synthases are implicated in IS pathology and their activity is regulated, inter alia, by various post-translational modifications and chromatin-based mechanisms. These account for heterogeneous alterations in NO production in a disease setting like IS. Interestingly, NO per se has been posited as an endogenous epigenetic modulator. Further, there is compelling evidence for an ingenious crosstalk between NO and HS in effecting the canonical (direct) and non-canonical (off-target collateral) functions. In this regard, NO-mediated S-nitrosylation and HS-mediated S-sulfhydration of specific reactive thiols in an expanding array of target proteins are the principal modalities mediating the all-pervasive influence of NO and HS on cell fate in an ischemic brain. An integrated stress response subsuming unfolded protein response and autophagy to cellular stressors like endoplasmic reticulum stress, in part, is entrenched in such signaling modalities that substantiate the role of NO and HS in priming the cells for stress response. The precis presented here provides a comprehension on the multifarious actions of NO and HS and their epigenetic underpinnings, their crosstalk in maintenance of cerebrovascular homeostasis, and their "Janus bifrons" effect in IS milieu together with plausible therapeutic implications.

Citing Articles

Unveiling Smyd-2's Role in Cytoplasmic Nrf-2 Sequestration and Ferroptosis Induction in Hippocampal Neurons After Cerebral Ischemia/Reperfusion.

Liu D, Zhu Y Cells. 2024; 13(23).

PMID: 39682718 PMC: 11639856. DOI: 10.3390/cells13231969.


A meta-analysis of animal studies evaluating the effect of hydrogen sulfide on ischemic stroke: is the preclinical evidence sufficient to move forward?.

Emre Aydingoz S, Teimoori A, Orhan H, Demirtas E, Zeynalova N Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(12):9533-9548.

PMID: 39017715 PMC: 11582254. DOI: 10.1007/s00210-024-03291-5.


Hydroxytyrosol, a Promising Supplement in the Management of Human Stroke: An Exploratory Study.

Naranjo A, Alvarez-Soria M, Aranda-Villalobos P, Martinez-Rodriguez A, Martinez-Lara E, Siles E Int J Mol Sci. 2024; 25(9).

PMID: 38732018 PMC: 11084205. DOI: 10.3390/ijms25094799.


TRIM59 suppresses the brain ischaemia/reperfusion injury and pyroptosis of microglial through mediating the ubiquitination of NLRP3.

Zhang L, Li G, Li Y Sci Rep. 2024; 14(1):2511.

PMID: 38291200 PMC: 10828378. DOI: 10.1038/s41598-024-52914-7.


Homocysteine and mitochondrial quality control in diabetic retinopathy.

Malaviya P, Kowluru R Eye Vis (Lond). 2024; 11(1):5.

PMID: 38229140 PMC: 10790378. DOI: 10.1186/s40662-023-00362-1.


References
1.
Jiang Z, Li C, Manuel M, Yuan S, Kevil C, McCarter K . Role of hydrogen sulfide in early blood-brain barrier disruption following transient focal cerebral ischemia. PLoS One. 2015; 10(2):e0117982. PMC: 4335059. DOI: 10.1371/journal.pone.0117982. View

2.
Chan S, Chai C, Lim T, Yamamoto M, Lo E, Lai M . Cystathionine β-synthase inhibition is a potential therapeutic approach to treatment of ischemic injury. ASN Neuro. 2015; 7(2). PMC: 4397212. DOI: 10.1177/1759091415578711. View

3.
Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Modis K, Panopoulos P . Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci U S A. 2012; 109(23):9161-6. PMC: 3384190. DOI: 10.1073/pnas.1202916109. View

4.
Sen N, Snyder S . Neurotrophin-mediated degradation of histone methyltransferase by S-nitrosylation cascade regulates neuronal differentiation. Proc Natl Acad Sci U S A. 2011; 108(50):20178-83. PMC: 3250167. DOI: 10.1073/pnas.1117820108. View

5.
Bardai F, Price V, Zaayman M, Wang L, DMello S . Histone deacetylase-1 (HDAC1) is a molecular switch between neuronal survival and death. J Biol Chem. 2012; 287(42):35444-35453. PMC: 3471765. DOI: 10.1074/jbc.M112.394544. View