Adaptive regulation of riboflavin transport in heart: effect of dietary riboflavin deficiency in cardiovascular pathogenesis
Deficiency or defective transport of riboflavin (RF) is known to cause neurological disorders, cataract, cardiovascular anomalies, and various cancers by altering the biochemical pathways. Mechanisms and regulation of RF uptake process is well characterized in the cells of intestine, liver, kidney, and brain origin, while very little is known in the heart. Hence, we aimed to understand the expression and regulation of RF transporters (rRFVT-1 and rRFVT-2) in cardiomyocytes during RF deficiency and also investigated the role of RF in ischemic cardiomyopathy and mitochondrial dysfunction in vivo. Riboflavin uptake assay revealed that RF transport in H9C2 is (1) significantly higher at pH 7.5, (2) independent of Na+ and (3) saturable with a Km of 3.746 µM. For in vivo studies, male Wistar rats (110–130 g) were provided riboflavin deficient food containing 0.3 ± 0.05 mg/kg riboflavin for 7 weeks, which resulted in over expression of both RFVTs in mRNA and protein level. RF deprivation resulted in the accumulation of cardiac biomarkers, histopathological abnormalities, and reduced mitochondrial membrane potential which evidenced the key role of RF in the development of cardiovascular pathogenesis. Besides, adaptive regulation of RF transporters upon RF deficiency signifies that RFVTs can be considered as an effective delivery system for drugs against cardiac diseases.
KeywordsRiboflavin Homocysteine Mitochondrial dysfunction Cardiovascular diseases
BA acknowledges DBT-RGYI, INDIA for the financial support [No. BT/PR15134/GBD/27/330/2011] and ICMR, India for the International Biomedical Scientists Fellowship (No. INDO/FRC/452/(Y83)/2016-17-IHD). TU thank DST-PURSE, MKU for the fellowship. Authors gratefully acknowledge DST-PURSE Program (India), Madurai Kamaraj University for the infrastructure and facilities.
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Conflict of interest
Authors have no conflict to declare in this research.
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