Expression of myo-inositol oxygenase in tissues susceptible to diabetic complications

Abstract

Alterations of intracellular levels of myo-inositol (MI) have the potential to impact such cellular processes as signaling pathways and osmotic balance. Depletion of MI has been implicated in the etiology of diabetic complications; however, the mechanistic details remain sketchy. myo-Inositol oxygenase (MIOX-EC 1.13.99.1) catalyzes the first committed step of the only pathway of MI catabolism. In the present study, extra-renal tissues and cell types, including those affected by diabetic complications, were examined for MIOX expression. Western blotting results indicated that kidney is the only major organ where MIOX protein is expressed at detectable levels. Immunohistochemical examination of the kidney revealed that the proximal tubular epithelial cells are the only site of MIOX expression in the kidney. Reverse-transcription-polymerase chain reaction (RT-PCR) and Western immunoblot analyses, however, revealed that the cell lines ARPE-19 and HLE-B3, representing human retinal pigmented epithelium and lens epithelium, respectively, also express MIOX. In addition, quantitative real-time RT-PCR analysis of all major tissues in the mouse showed that the sciatic nerve contained MIOX transcript, which was found to be significantly higher than that observed in other non-renal organs. These results indicate that MIOX is found at lower levels in extra-renal tissues where diabetic complications, including nephropathy, neuropathy, retinopathy, and cataract, are frequently observed.