CSN1S1 and CSN3 gene variants in female Murrah buffaloes in the Brazilian Amazon.

The characteristics of milk are controlled by several genes, with emphasis on the four genes from casein, CSN1S1; CSN1S2; CSN2 and CSN3, which are responsible encoding of fractions the milk protein. The study of genetic variants in these genes, seek to investigate alleles, insertions or deletions, that can directly reflect on productive characteristics, indicating differences in milk quality, composition and yield. The CSN1S1 and CSN3 genes were analyzed in lactating Murrah buffaloes using nucleotide sequencing. An SNP was found in the amplified fragment of the CSN1S1 gene, located in nucleotide number 2,123 of the promoter region in position nt-258 (A/G). As for the CSN3 gene, two SNPs of exon number 4 were identified in codons 33 (ACC/ATC) and 34 (ACC/ACT) of the analyzed fragment. This study contributes to important associations between genetic variants and the desired characteristics of milk and its derivatives in future studies, because the variants found may be associated with the quality of milk, enabling genetic selection to be assisted by molecular markers, indicating a major advance that makes it possible to select animals early.

Deregulation of mitochondrial functions provoked by long-chain fatty acid accumulating in long-chain 3-hydroxyacyl-CoA dehydrogenase and mitochondrial permeability transition deficiencies in rat heart--mitochondrial permeability transition pore opening as a potential contributing pathomechanism of cardiac alterations in these disorders.

Mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies are fatty acid oxidation disorders biochemically characterized by tissue accumulation of long-chain fatty acids and derivatives, including the monocarboxylic long-chain 3-hydroxy fatty acids (LCHFAs) 3-hydroxytetradecanoic acid (3HTA) and 3-hydroxypalmitic acid (3HPA). Patients commonly present severe cardiomyopathy for which the pathogenesis is still poorly established. We investigated the effects of 3HTA and 3HPA, the major metabolites accumulating in these disorders, on important parameters of mitochondrial homeostasis in Ca(2+) -loaded heart mitochondria. 3HTA and 3HPA significantly decreased mitochondrial membrane potential, the matrix NAD(P)H pool and Ca(2+) retention capacity, and also induced mitochondrial swelling. These fatty acids also provoked a marked decrease of ATP production reflecting severe energy dysfunction. Furthermore, 3HTA-induced mitochondrial alterations were completely prevented by the classical mitochondrial permeability transition (mPT) inhibitors cyclosporin A and ADP, as well as by ruthenium red, a Ca(2+) uptake blocker, indicating that LCHFAs induced Ca(2+)-dependent mPT pore opening. Milder effects only achieved at higher doses of LCHFAs were observed in brain mitochondria, implying a higher vulnerability of heart to these fatty acids. By contrast, 3HTA and docosanoic acids did not change mitochondrial homeostasis, indicating selective effects for monocarboxylic LCHFAs. The present data indicate that the major LCHFAs accumulating in mitochondrial trifunctional protein and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies induce mPT pore opening, compromising Ca(2+) homeostasis and oxidative phosphorylation more intensely in the heart. It is proposed that these pathomechanisms may contribute at least in part to the severe cardiac alterations characteristic of patients affected by these diseases.