Molecular and Cellular Biochemistry

, Volume 440, Issue 1–2, pp 147–156 | Cite as

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

  • Tamilarasan Udhayabanu
  • Sellamuthu Karthi
  • Ayyavu Mahesh
  • Perumal Varalakshmi
  • Andreea Manole
  • Henry Houlden
  • Balasubramaniem Ashokkumar


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.


Riboflavin 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.

Compliance with ethical standards

Conflict of interest

Authors have no conflict to declare in this research.

Supplementary material

11010_2017_3163_MOESM1_ESM.jpg (101 kb)
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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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Genetic Engineering, School of BiotechnologyMadurai Kamaraj UniversityMaduraiIndia
  2. 2.Centre for Excellence in Genomics Science, School of Biological SciencesMadurai Kamaraj UniversityMaduraiIndia
  3. 3.Department of Molecular Microbiology, School of BiotechnologyMadurai Kamaraj UniversityMaduraiIndia
  4. 4.Department of Molecular Neuroscience and Neurogenetics LaboratoryUCL Institute of Neurology, Queen SquareLondonUK

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