Biotin Regulates the Genetic Expression of Holocarboxylase Synthetase and Mitochondrial Carboxylases in Rats

Abstract

Biotin is the cofactor of carboxylases [pyruvate (PC), propionyl-CoA (PCC), 3-methyl crotonyl-CoA and acetyl-CoA], to which it is covalently bound by the action of holocarboxylase synthetase (HCS). We have studied whether biotin also regulates their expression, as it does other, nonrelated enzymes (e.g., glucokinase, phosphoenol pyruvate carboxykinase, guanylate cyclase). For this purpose, HCS, PC and PCC mRNAs were studied in biotin-deficient rat liver, kidney, muscle and brain of biotin-deficient rats. PC- and PCC-specific activities and protein masses were also measured. The 24-h time course of HCS mRNA in deficient rats was examined after biotin supplementation. HCS mRNA was significantly reduced during vitamin deficiency. It increased in deficient rats after biotin was injected, reaching control levels 24 h after administration. These changes seem to be the first known instance in mammals of an effect of a water-soluble vitamin on a mRNA functionally related to it. In contrast, the decreased activities of the carboxylases were associated with reductions in the amounts of their enzyme proteins except in brain. However, their mRNA levels were not affected. There are no reports on these types of vitamin affecting the mRNA or protein levels of their apoenzymes or their products. This work provides evidence for biotin being a modulator of the genetic expression of the enzymes involved in its function as a cofactor. As such, it may be a useful model for probing a similar role for other water-soluble vitamins.

MicroRNA-539 Is Up-regulated in Failing Heart, and Suppresses O-GlcNAcase Expression

“…KIT or c-kit) represses miR-539 expression, thereby de-repressing microphthalmia-associated transcription factor expression and promoting proliferation (43). In other cell types, miR-539 expression may be biotin-sensitive, and miR-539 targets the mRNA of holocarboxylase synthase, which participates in genetic stability (44). Such collective findings create interesting implications for a more detailed understanding of the molecular interactions governing O-GlcNAc-dependent cell function; however, there is no evidence, at present to directly link the aforementioned observations to one another, at least at the level of O-GlcNAcylation.…”

Biotin Supplementation Increases Expression of Genes Encoding Interferon-γ, Interleukin-1β, and 3-Methylcrotonyl-CoA Carboxylase, and Decreases Expression of the Gene Encoding Interleukin-4 in Human Peripheral Blood Mononuclear Cells

“…To confirm integrity of RNA, 22 g of RNA were electrophoresed using a formaldehyde-agarose gel (22); RNA was stained with ethidium bromide and visualized using a Kodak EDAS 290 Documentation and Analysis System (Rochester, NY). Two major ribosomal bands (28S and 18S rRNA) but no degraded RNA were detected (data not shown).…”

Effect of Biotin Treatment on Hepatic Gene Expression in Streptozotocin-Induced Diabetic Rats

“…25) Furthermore, the mRNA expression of the biotin transporter sodiumdependent multivitamin transporter (SMVT) and pyruvate carboxylase was also decreased in biotin-deficient rat liver and human leukocytes. [26][27][28][29][30] In addition to these genes, the mRNA level of biotinidase was analyzed by quantitative RT-PCR. The abundance of mRNAs of HCS and SMVT remained unchanged by the biotin treatment in STZ rats (Fig.…”