a-lipoic-acid decreases O-GlcNAcylation in diabetic liver

What is it about?

The effects of treatment with α-lipoic acid (LA), a naturally occurring compound possessing antioxidant activity, on liver oxidant stress in a rat model of streptozotocin (STZ)-induced diabetes, were investigated by examining potential mechanistic points that influence changes in expression of the antioxidant enzymes catalase (CAT) and CuZn-/Mn- superoxide dismutase(s) (SOD). LA was administered for four weeks by daily intraperitoneal injections (10 mg/kg) to STZ-induced diabetic rats, starting from the last STZ treatment. LA administration practically normalized the activities of the indicators of hepatocellular injury, alanine- and aspartate aminotransferases, and lowered oxidative stress, observed by the TBARS assay, as a restored GSH/GSSG ratio and increased protein sulfhydryl group content. The lower level of DNA damage detected by the Comet assay, revealed that LA lessened cytotoxic signalling, exerting a hepatoprotective effect. LA-treated diabetic rats displayed restored specific enzymatic activities of CAT, CuZnSOD and MnSOD. qRT-PCR analysis showed that LA restored CAT gene expression to its physiological level and increased CuZnSOD gene expression, however, MnSOD gene expression remained at the diabetic level. Whereas the amounts of CAT and CuZnSOD proteins returned to the control levels, MnSOD protein was elevated. These results suggest that LA administration affected CAT and CuZnSOD expression mainly at the transcriptional, and MnSOD expression at the posttranscriptional level. The observed LA-promoted decrease of O-GlcNAcylation of ERK, p38 kinase, NF-κB, C/EBPβ, and of the antioxidative enzymes themselves in diabetic rats, suggests that the regulatory mechanisms which supported the changes in antioxidative enzyme expression were also influenced by posttranslational mechanisms.

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