[Study of high selenium interfering with glucose and one-carbon metabolism in hepatocytes in vitro].

Abstract

Objective: To investigate the effects of high selenium environment on the expression of selenoproteins and enzymes related to glucose and one-carbon metabolism in normal human hepatocytes.

Methods: Ten different concentrations of selenomethionine(SeMet, 0, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5 and 10 μmol/L) was added into the normal human hepatocyts and incubated for 48 hours. The expressions of selenoprotein(GPX1 and SELENOP1) and metabolic enzymes(PHGDH, SHMT1, MTHFR and MS) were analyzed by Western blot.

Results: When the concentration of SeMet was 0-10 μmol/L, the expression trend of selenoprotein(GPX1 and SELENOP1) is similar, which first increases and then decreases. There is a slight difference between the inflection points of GPX1 and SELENOP1, which are respectively 0.5 μmol/L and 0.1 μmol/L. The expression trend of serine de novo synthesis pathway key enzymes(PHGDH) and folate cycle metabolizing enzymes(SHMT1, MTHFR and MS) is similar to that of selenoproteins, which also increases first and then decreases, but the inflection points are different, which are respectively 0.1 μmol/L(PHGDH and SHMT1) and 0.01 μmol/L(MTHFR and MS).

Conclusion: Under the high selenium environment, the glycolytic bypass-serine de novo synthesis pathway is activated to synthesize endogenous serine due to the insufficient intracellular serine supply, causing abnormal glucose metabolism, which is an important extension to the hypothesis of the molecular mechanism of high selenium causing IR.