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

Brown−Vialetto−Van Laere and Fazio−Londe syndromes: SLC52A3 mutations with puzzling phenotypes and inheritance

BACKGROUND: Brown-Vialetto-Van Laere Syndrome (BVVLS) and Fazio-Londe Disease (FLD) are rare neurological disorders presenting with pontobulbar palsy, muscle weakness, and respiratory insufficiency. Mutations in SLC52A2 (hRFVT-2) or SLC52A3 (hRFVT-3) genes can be responsible for these disorders with an autosomal recessive pattern of inheritance. The aim of this study is to screen for mutations in SLC52A2 and SLC52A3 among Indian families diagnosed with BVVLS and FLD. METHODS: SLC52A2 and SLC52A3 were screened in one FLD and three BVVLS patients by exon-specific amplification using PCR and sequencing. In silico predictions using bioinformatics tools and confocal imaging using HEK-293 cells were performed to determine the functional impact of identified mutations. RESULTS: Genetic analysis of a mother and son with BVVLS was identified with a novel homozygous mutation c.710C>T (p.Ala237Val) in SLC52A3. This variant was found to have autosomal pseudo-dominant pattern of inheritance, which was neither listed in the Exome variant server or in 1000 genomes database. In silico analysis and confocal imaging of the p.Ala237Val variant showed higher degree of disorderness in hRFVT3 that could affect riboflavin transport. Furthermore, a common homozygous mutation c.62A>G (p.Asn21Ser) was identified in other BVVLS and FLD patients. Despite having different clinical phenotypes, both BVVLS and FLD disorder can be attributed to this mutation. CONCLUSION: A rare and peculiar pattern of autosomal pseudo-dominant inheritance is observed for the first time in two genetically related BVVLS cases with Indian origin and a common mutation c.62A>G (p.Asn21Ser) in SLC52A3 can be responsible for both BVVLS and FLD with variable phenotypes

Metallothermic reduction of zinc sulfide induced by ball milling

© 2017, Springer Science+Business Media New York. Stoichiometric mixtures of ZnS + Al and ZnS + Mg were milled for different times in a planetary ball mill. The XRD traces of the as-milled samples showed the presence of zinc, MgZn2, and MgS after 30-min milling in the ZnS–Mg system. The traces of MgZn2disappeared after 1-h milling and the reduction reaction seemed to have been completed after 5-h milling. The ZnS–Al system was somewhat different with only slight reduction to zinc after 1 h and ZnS peaks still present after 10 h of milling. Isothermal heating under argon atmosphere of 3-h-milled samples showed the presence of hexagonal ZnAl2S4and mixtures of MgS and Zn0.68Mg0.32S in the ZnS–Al and ZnS–Mg systems, respectively. These results show that the reaction in the ZnS–Al system progressed gradually during milling. The decrease in the crystallite size of reactants materials (especially ZnS) during milling operation led to decrease in the formation temperature of hexagonal ZnAl2S4phase and decrease in the transformation temperature of sphalerite (ZnS) to hexagonal wurtzite