ArticleAntioxidants & redox signaling2014
CaMKKβ-dependent activation of AMP-activated protein kinase is critical to suppressive effects of hydrogen sulfide on neuroinflammation.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review.International journal of molecular sciences · 2025Pooled it
- Unlocking the gasotransmitter: hydrogen sulfide as a multitarget regulator in ischemia-reperfusion injury.Medical gas research · 2026Review
- AMPK Therapy-A Little Goes A Long Way.Cells · 2026Review
- Hydrogen Sulfide Rescues Microglia From HIV Tat-Driven Ferroptosis: Implications for HIV-Associated Neuroinflammation.CNS neuroscience & therapeutics · 2026Article
- Paeonol Mitigates Neurodegeneration: Molecular Insights into Its Anti-inflammatory, Antioxidant, and Synaptoprotective Mechanisms.Molecular neurobiology · 2025Review
- Aging-Induced Episodic-Like Memory Impairment Could be Alleviated by Melatonin Treatment via Preserving Blood-Brain Barrier Integrity and Upregulating CRTC1.CNS neuroscience & therapeutics · 2025Article
- Fluoride-induced Neurodevelopmental Toxicity- AMPK as a Possible Target.CNS & neurological disorders drug targets · 2025Review
- Microglia-induced neuroinflammation in hippocampal neurogenesis following traumatic brain injury.Heliyon · 2024Review
- ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis.Frontiers of medicine · 2023Article
- HMolecular neurobiology · 2023Review
- Protective Effect of Hydrogen Sulfide on Cerebral Ischemia-Reperfusion Injury.Cellular and molecular neurobiology · 2023Review
- Correction: La Torre et al. Role of Vitamin E and the Orexin System in Neuroprotection.Brain sciences · 2022Article
- Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.International immunopharmacology · 2022Article
- Emerging roles of cystathionine β-synthase in various forms of cancer.Redox biology · 2022Review
- Bioresponsive nano-antibacterials for HScience advances · 2022Article
- Activation of UCP2 by anethole trithione suppresses neuroinflammation after intracerebral hemorrhage.Acta pharmacologica Sinica · 2022Article
- A Novel Pyrazolo[3,4-Molecules and cells · 2022Article
- Hydrogen Sulfide Attenuates the Cognitive Dysfunction in Parkinson's Disease Rats via Promoting Hippocampal Microglia M2 Polarization by Enhancement of Hippocampal Warburg Effect.Oxidative medicine and cellular longevity · 2022Article
- Ramelteon Ameliorates LPS-Induced Hyperpermeability of the Blood-Brain Barrier (BBB) by Activating Nrf2.Inflammation · 2021Article
- Role of Vitamin E and the Orexin System in Neuroprotection.Brain sciences · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsThe manner in which hydrogen sulfide (H2S) suppresses neuroinflammation is poorly understood. We investigated whether H2S polarized microglia to an anti-inflammatory (M2) phenotype by activating AMP-activated protein kinase (AMPK).
resultsThree structurally unrelated H2S donors (5-(4-hydroxyphenyl)-3H-1,2-dithiocyclopentene-3-thione [ADT-OH], (p-methoxyphenyl) morpholino-phosphinodithioic acid [GYY4137], and sodium hydrosulfide [NaHS]) enhanced AMPK activation in BV2 microglial cells in the presence and absence of lipopolysaccharide (LPS). The overexpression of the H2S synthase cystathionine β-synthase (CBS) in BV2 cells enhanced endogenous H2S production and AMPK activation regardless of LPS stimulation. On LPS stimulation, overexpression of both ADT-OH and CBS promoted M2 polarization of BV2 cells, as evidenced by suppressed M1 and elevated M2 signature gene expression. The promoting effects of ADT-OH on M2 polarization were attenuated by an AMPK inhibitor or AMPK knockdown. Liver kinase B1 (LKB1) and calmodulin-dependent protein kinase kinase β (CaMKKβ) are upstream kinases that activate AMPK. ADT-OH activated AMPK in Hela cells lacking LKB1. In contrast, both the CaMKKβ inhibitor and siRNA abolished ADT-OH activation of AMPK in LPS-stimulated BV2 cells. Moreover, the CaMKKβ inhibitor and siRNA blunted ADT-OH suppression on M1 gene expression and enhancement of M2 gene expression in LPS-stimulated BV2 cells. Moreover, ADT-OH promoted M2 polarization of primary microglia in an AMPK activation- and CaMKKβ-dependent manner. Finally, in an LPS-induced in vivo neuroinflammation model, both ADT-OH and NaHS enhanced AMPK activation in the brain area where microglia were over-activated on LPS stimulation. Furthermore, ADT-OH suppressed M1 and promoted M2 gene expression in this in vivo model. INNOVATION AND
conclusionCaMKKβ-dependent AMPK activation is an unrecognized mechanism underlying H2S suppression on neuroinflammation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.