Abstract
Hydrogen sulfide (H2S), a mammalian gasotransmitter, is involved in the regulation of a variety of fundamental processes including intracellular signaling, cellular bioenergetics, cell proliferation, and cell differentiation. Cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST) are currently considered the three principal mammalian H2S-generating enzymes. However, recently, a fourth H2S-producing enzyme, selenium-binding-protein 1 (SELENBP1), has also been identified. The cellular regulatory role(s) of SELENBP1 are incompletely understood. The current study investigated whether SELENBP1 plays a role in the regulation of adipocyte differentiation in vitro. 3T3-L1 preadipocytes with or without SELENBP1 knock-down were subjected to differentiation-inducing conditions, and H2S production, cellular lipid accumulation, cell proliferation, and mitochondrial activity were quantified. Adipocyte differentiation was associated with an upregulation of H2S biosynthesis. SELENBP1 silencing decreased cellular H2S levels, suppressed the expression of the three “classical” H2S-producing enzymes (CBS, CSE, and 3-MST) and significantly suppressed adipocyte differentiation. Treatment of SELENBP1 knock-down cells with the H2S donor GYY4137 partially restored lipid accumulation, increased cellular H2S levels, and exerted a bell-shaped effect on cellular bioenergetics (enhancement at 1 and 3 mM, and inhibition at 6 mM). We conclude that SELENBP1 in adipocytes (1) contributes to H2S biosynthesis and (2) acts as an endogenous stimulator of adipocyte differentiation.
Highlights
Over the last two decades, the gaseous mediator hydrogen sulfide (H2 S) has emerged as a mammalian, diffusible mediator, with important roles in the regulation of fundamental cellular functions in health and disease
SELENBP1 was upregulated in similar to those of the control (shCtr), to the results obtained in wild type cells
Differentiated shCtr and sh85 displayed comparable proliferation rates, which were similar to rates of the non-differentiated sh86 cells. These results suggests that SELENBP1 affects cell proliferation both in the undifferentiated cells (3T3-L1, D0) as well as in the mature adipocytes (D7)
Summary
Over the last two decades, the gaseous mediator hydrogen sulfide (H2 S) has emerged as a mammalian, diffusible mediator, with important roles in the regulation of fundamental cellular functions in health and disease. H2 S generated by these enzymes acts as a labile, diffusible mediator. It reaches various cellular compartments; it can exit the cell to exert autocrine and paracrine biological actions. The potential regulation and cellular function by these more recently identified biological H2 S sources is incompletely understood
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