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Reprogramming of Colonic Cell Metabolism by H 2 S
Author(s) -
Vitvitsky Victor,
Libiad Marouane,
Bostelaar Trever,
Maebius Allison,
Lee HoJoon,
Lyssiotis Costas A.,
Banerjee Ruma
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.485.11
Subject(s) - chemistry , metabolism , cell growth , biochemistry , enzyme , glycolysis , respiration , cell culture , biology , botany , genetics
Synthesis of H 2 S by gut microbiota leads to routine colonic cells exposure to this respiratory toxin. Herein we studied the effect of H 2 S on metabolism and proliferation in human colonic cells in culture at sulfide concentrations up to 300 μM, which represents a physiologically relevant exposure for these cells. H 2 S caused a marked activation of glycolysis and inhibition of proliferation. Between 5–20 μM H 2 S the oxygen consumption rate (OCR) was activated, while OCR was inhibited at higher concentrations. A high‐capacity mitochondrial sulfide oxidation pathway housed in colonocytes supports O 2 ‐dependent H 2 S clearance and the absence of the committing enzyme (sulfide quinone reductase) in the pathway leads to inhibition of OCR even at the lowest H 2 S concentration that was tested. H 2 S triggers persulfidation of numerous protein targets that are enriched in energy metabolism pathways. The antiproliferative effect of H 2 S exposure results from electron acceptor insufficiency that ensues from H 2 S oxidation activity and inhibition of respiration. Under these conditions, reductive carboxylation of a‐ketoglutarate is enhanced and exogenous uridine and aspartate alleviated H 2 S‐imposed growth restriction. Overexpression of the sulfide oxidation enzymes in colon cancer tissue and cells confers a growth advantage during H 2 S exposure compared to non‐malignant cells. These results predict that the stress response in colonocytes triggered by microbial H 2 S exposure involves metabolic reprogramming to recycle electron acceptors. Support or Funding Information NIH (GM112455 to R.B.), AACR NextGen Grant for Transformative Cancer Research (17‐20‐01‐LYSS) to C.A.L., UMCCC Core Grant (P30 CA046592) to R.B. and C.A.L. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .