H2S-induced S-sulfhydration of lactate dehydrogenase A (LDHA) stimulates cellular bioenergetics in HCT116 colon cancer cells.

H2S-induced S-sulfhydration of lactate dehydrogenase A (LDHA) stimulates cellular bioenergetics in HCT116 colon cancer cells. Biochem Pharmacol. 2017 Apr 09;: Authors: Untereiner AA, Oláh G, Módis K, Hellmich MR, Szabo C Abstract Cystathionine-β-synthase (CBS) is upregulated and hydrogen sulfide (H2S) production is increased in colon cancer cells. The functional consequence of this response is stimulation of cellular bioenergetics and tumor growth and proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various colon cancer cells and has been previously implicated in tumor cell bioenergetics and proliferation. In the present study, we sought to determine the potential interaction between the H2S pathway and LDH activity in the control of bioenergetics and proliferation of colon cancer, using the colon cancer line HCT116. Low concentrations of GYY4137 (a slow-releasing H2S donor) enhanced mitochondrial function (oxygen consumption, ATP production, and spare respiratory capacity) and glycolysis in HCT116 cells. SiRNA-mediated transient silencing of LDHA attenuated the GYY4137-induced stimulation of mitochondrial respiration, but not of glycolysis. H2S induced the S-sulfhydration of Cys163 in recombinant LDHA, and stimulated LDHA activity. The H2S-induced stimulation of LDHA activity was absent in C163A LDHA. As shown in HCT116 cell whole extracts, in addition to LDHA activation, GYY4137 also stimulated LDHB activity,...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research