Posterpreis - Ageing Meeting Halle 2023

11th International Meeting on Ageing: "Modifying Cardiovascular Ageing: from old cells to elderly patients” 

HYDROGEN SULFIDE (H2S) PRODUCTION BY SELENIUM-BINDING PROTEIN 1:
SELENBP1 IS A COPPER-DEPENDENT THIOL OXIDASE

TM Philipp, AS Scheller, A Kipp, H Steinbrenner, LO Klotz
Institute of Nutritional Sciences, Nutrigenomics, Friedrich Schiller University, Jena

Abstract

Introduction: As our population is progressively aging, we notice an increasing number of patients who suffer from diseases asso-ciated with old age such as cancer. The gasotransmitter hydrogen sulfide (H₂S) has been proposed to promote tumor growth. In human colorectal cancer biopsies, elevated H2S levels have been detected, resulting from selective up-regulation of the H₂S-generating enzyme, cystathionine β-synthase (CBS). In contrast to CBS, another H₂S-producing enzyme, selenium-binding protein 1 (SELENBP1), is largely down-regulated in many tumors. SELENBP1 is considered a novel player in sulfur biochemistry, based on its recently discovered capability to convert methanethiol to H₂S.
Results: We found that mRNA and protein levels of SELENBP1 and CBS were reciprocally regulated during spontaneous differentiation of Caco-2 human colorectal adenocarcinoma cells to a colonocyte-like phenotype. In parallel with elevated SELENBP1 levels, we detected a strong increase in methanethiol oxidase (MTO) activity during differentiation of Caco-2 cells. Analysis of recombinant SELENBP1 revealed that its MTO activity is copper-dependent, whereas selenium is dispensable. Moreover, we observed that SELENBP1 is capable of metabolizing multiple alkyl thiols beside methanethiol, showing a gradual decrease in oxidation rate with increasing chain length and polarity. The substrates for SELENBP1-catalyzed H₂S production might not exclusively be derived from microbial sources or from the diet, as the enzyme methyltransferase-like 7B (METTL7B) has been reported to endogenously generate methanethiol. Indeed, we detected METTL7B gene expression in various human cell lines from different origins.