Subtopic Deep Dive

Hydrogen Sulfide Cell Signaling
Research Guide

What is Hydrogen Sulfide Cell Signaling?

Hydrogen sulfide cell signaling refers to the physiological roles of H2S as an endogenous gasotransmitter regulating processes like vascular relaxation, neuroprotection, protein sulfhydration, and angiogenesis through enzymatic production and specific molecular targets.

H2S is produced in mammalian cells by enzymes such as cystathionine-β-synthase and acts alongside NO and CO as a third gasotransmitter (Wang, 2002; 1789 citations). Key mechanisms include sulfhydration of proteins and crosstalk with nitric oxide in angiogenesis and vasorelaxation (Coletta et al., 2012; 668 citations). Over 10 major papers from 2002-2020 explore its production pathways, therapeutic potential, and roles in cancer and cardiovascular disease.

Curated Papers

Key Challenges

Why It Matters

H2S signaling drives vascular relaxation and angiogenesis, offering therapeutic targets for cardiovascular diseases like endothelial dysfunction (Sun et al., 2020; 512 citations; Wallace and Wang, 2015; 835 citations). In cancer, tumor-derived H2S from cystathionine-β-synthase promotes bioenergetics, proliferation, and angiogenesis in colon cancer cells (Szabó et al., 2013; 733 citations). These pathways enable H2S donors as novel drugs for inflammation, neuroprotection, and oncology (Powell et al., 2017; 565 citations).

Key Research Challenges

H2S Detection Specificity

Accurate measurement of H2S in cells is hindered by its reactivity and rapid diffusion, complicating distinction from other sulfur species. Current probes lack selectivity amid biological interferents (Wang, 2012; 1876 citations). Novel donors and sensors are needed for precise signaling studies (Powell et al., 2017).

Enzyme Regulation Mechanisms

Pathways like D-cysteine metabolism by 3-mercaptopyruvate sulfurtransferase challenge understanding of non-canonical H2S production (Shibuya et al., 2013; 540 citations). Variability in cystathionine-β-synthase activity across tissues remains unclear (Szabó et al., 2013). Integrating genomic and proteomic data is essential.

Gasotransmitter Crosstalk

Mutual dependence between H2S and NO in angiogenesis requires dissecting synergistic vs. independent effects (Coletta et al., 2012; 668 citations). Context-specific roles in pathology like cancer complicate therapeutic design (Szabó, 2015; 682 citations). Quantitative modeling of interactions is lacking.

Essential Papers

Physiological Implications of Hydrogen Sulfide: A Whiff Exploration That Blossomed

Rui Wang · 2012 · Physiological Reviews · 1.9K citations

The important life-supporting role of hydrogen sulfide (H 2 S) has evolved from bacteria to plants, invertebrates, vertebrates, and finally to mammals. Over the centuries, however, H 2 S had only b...

Two's company, three's a crowd: can H <sub>2</sub> S be the third endogenous gaseous transmitter?

Rui Wang · 2002 · The FASEB Journal · 1.8K citations

Bearing the public image of a deadly “gas of rotten eggs,” hydrogen sulfide (H 2 S) can be generated in many types of mammalian cells. Functionally, H 2 S has been implicated in the induction of hi...

Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter

John L. Wallace, Rui Wang · 2015 · Nature Reviews Drug Discovery · 835 citations

Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer

Csaba Szabó, Ciro Coletta, Celia Chao et al. · 2013 · Proceedings of the National Academy of Sciences · 733 citations

The physiological functions of hydrogen sulfide (H 2 S) include vasorelaxation, stimulation of cellular bioenergetics, and promotion of angiogenesis. Analysis of human colon cancer biopsies and pat...

Gasotransmitters in cancer: from pathophysiology to experimental therapy

Csaba Szabó · 2015 · Nature Reviews Drug Discovery · 682 citations

Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation

Ciro Coletta, Andreas Papapetropoulos, Katalin Erdélyi et al. · 2012 · Proceedings of the National Academy of Sciences · 668 citations

Hydrogen sulfide (H 2 S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H 2 S (stimulation of angiogenesis, r...

A review of hydrogen sulfide (H2S) donors: Chemistry and potential therapeutic applications

Chadwick R. Powell, Kearsley M. Dillon, John B. Matson · 2017 · Biochemical Pharmacology · 565 citations

Reading Guide

Foundational Papers

Start with Wang (2002; 1789 citations) for gasotransmitter concept and Wang (2012; 1876 citations) for comprehensive physiology; then Coletta et al. (2012; 668 citations) for H2S-NO interactions.

Recent Advances

Sun et al. (2020; 512 citations) links H2S to endothelial dysfunction; Powell et al. (2017; 565 citations) reviews donors for therapeutics.

Core Methods

Enzyme assays for CBS activity, sulfhydration via biotin-switch, H2S donors like GYY4137, and live-cell imaging with fluorescent probes (Powell et al., 2017; Shibuya et al., 2013).

How PapersFlow Helps You Research Hydrogen Sulfide Cell Signaling

Discover & Search

Research Agent uses searchPapers with 'H2S gasotransmitter sulfhydration' to retrieve Wang (2012; 1876 citations), then citationGraph maps influencers like Coletta et al. (2012), and findSimilarPapers expands to cancer applications; exaSearch drills into 'H2S D-cysteine pathway' for Shibuya et al. (2013).

Analyze & Verify

Analysis Agent applies readPaperContent on Szabó et al. (2013) to extract CBS-H2S bioenergetics data, verifyResponse with CoVe cross-checks claims against Wang (2002), and runPythonAnalysis plots H2S concentration-response curves from extracted datasets using matplotlib; GRADE scores evidence strength for therapeutic claims.

Synthesize & Write

Synthesis Agent detects gaps in H2S-NO crosstalk post-Coletta et al. (2012), flags contradictions in cancer roles, then Writing Agent uses latexEditText for pathway diagrams, latexSyncCitations for 10+ references, and latexCompile to generate a review section; exportMermaid visualizes signaling cascades.

Use Cases

"Analyze H2S dose-response in colon cancer bioenergetics from Szabó 2013."

Analysis Agent → readPaperContent (Szabó et al., 2013) → runPythonAnalysis (pandas curve fitting, matplotlib plots) → GRADE quantitative claims → researcher gets fitted EC50 values and verification report.

"Draft LaTeX figure of H2S sulfhydration pathway with citations."

Synthesis Agent → gap detection (sulfhydration mechanisms) → Writing Agent → latexGenerateFigure (TikZ diagram) → latexSyncCitations (Wang 2012) → latexCompile → researcher gets compiled PDF with 5 cited papers.

"Find GitHub repos analyzing H2S signaling datasets."

Research Agent → paperExtractUrls (Wang 2012) → paperFindGithubRepo → githubRepoInspect (code review) → researcher gets 3 repos with simulation scripts for H2S kinetics.

Automated Workflows

Deep Research workflow scans 50+ H2S papers via searchPapers → citationGraph → structured report on gasotransmitter evolution (Wang 2002-2012). DeepScan's 7-steps verify crosstalk claims: readPaperContent (Coletta 2012) → CoVe → runPythonAnalysis correlations. Theorizer generates hypotheses on H2S donors from Powell (2017) + Szabó (2015).

Try Doxa for Hydrogen Sulfide Cell Signaling Research

Frequently Asked Questions

What defines H2S as a gasotransmitter?

H2S qualifies as a gasotransmitter due to enzymatic production in mammalian cells, membrane permeability, and regulated effects on hippocampal LTP and vascular tone (Wang, 2002; 1789 citations; Wang, 2003; 511 citations).

What are key H2S production methods?

Canonical enzymes include cystathionine-β-synthase; a novel pathway uses D-cysteine via 3-mercaptopyruvate sulfurtransferase (Shibuya et al., 2013; 540 citations; Szabó et al., 2013; 733 citations).

Which papers established H2S signaling?

Wang (2002; 1789 citations) proposed H2S as the third gasotransmitter; Wang (2012; 1876 citations) reviewed physiological roles across evolution (Wang, 2012).

What are open problems in H2S signaling?

Challenges include specific detection amid reactivity, dissecting H2S-NO synergies in angiogenesis, and context-dependent roles in cancer vs. therapy (Coletta et al., 2012; Szabó, 2015).