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Adaptive regulation of riboflavin transport in heart: effect of dietary riboflavin deficiency in cardiovascular pathogenesis

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Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, Madurai, 625021, India

    Tamilarasan Udhayabanu, Sellamuthu Karthi & Balasubramaniem Ashokkumar

  2. Centre for Excellence in Genomics Science, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India

    Ayyavu Mahesh

  3. Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, 625021, India

    Perumal Varalakshmi

  4. Department of Molecular Neuroscience and Neurogenetics Laboratory, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Andreea Manole & Henry Houlden

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  1. Tamilarasan Udhayabanu
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Correspondence to Balasubramaniem Ashokkumar.

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11010_2017_3163_MOESM1_ESM.jpg

Supplementary Figure S1: Qualitative assay to detect the presence of Cardiac Troponin-I. Control (A) and RF deficient (B) rat using Troponin-I test strip. The presence of band in the test region of RF deficient sample indicates that the concentration of Troponin-I is greater than 1.5 ng/mL. Supplementary material 1 (JPEG 100 kb)

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Udhayabanu, T., Karthi, S., Mahesh, A. et al. Adaptive regulation of riboflavin transport in heart: effect of dietary riboflavin deficiency in cardiovascular pathogenesis. Mol Cell Biochem 440, 147–156 (2018). https://doi.org/10.1007/s11010-017-3163-1

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