A genetic analysis of meat compositions in Japanese Black cattle: Genetic parameters and sex influence.

Meat composition in beef is related to eating quality and food functionality. Genetic parameters for several meat compositions including free amino acid, peptide and sugar, however, remain poorly described. In this study, we estimated genetic parameters for 51 meat components, including free amino acids, peptides, sugars and fatty acid compositions, and two carcase traits in 1,354 heifers and 1,797 steers of Japanese Black cattle. Heritability estimates were generally equivalent to or moderately greater than those in previous studies of this breed. Genetic correlations between free amino acids, peptides and sugars and carcase traits were often negative, suggesting a trade-off between traits. Using two-trait animal models that treat records from the two sexes as different traits, we estimated sex-specific heritabilities and cross-sex genetic correlations which indicate the sex differences in genetic architecture. In these analyses, 12 traits showed significant heritability differences between sexes and cross-sex genetic correlations occasionally deviated from unity. These results could be used to inform future breeding schemes and investigations of the genetic architecture of meat compositions in beef.

Endothelin-1 inhibits induction of nitric oxide synthase and GTP cyclohydrolase I in rat mesangial cells.

To investigate the interaction between endothelin (ET) and the nitric oxide system, we examined the effects of ET-1 and ET-3 on the induction of inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GTP:CHI), the rate-limiting enzyme of de novo synthesis of the cofactor tetrahydrobiopterin (BH4), in rat mesangial cells. ET-1 inhibited the nitrite accumulation induced by a combination of interleukin-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide in a concentration-dependent manner. The inhibitory effect of ET-3 was less potent than that of ET-1. A selective ETA antagonist, BQ-485, and an ETA and ETB antagonist, TAK-044, abolished the inhibitory effects of ET-1, whereas the selective ETB antagonist BQ-788 had no effect on the inhibition produced by ET-1. These observations indicate that ET-1 inhibits cytokine-stimulated nitrite accumulation through the ETA receptor. Western blot analysis showed that the suppression of nitrite accumulation was accompanied by a decrease in iNOS protein. Northern blot analysis showed that ET-1 inhibited the expression of both iNOS and GTP:CHI mRNA. In conclusion, ET-1 inhibits cytokine-stimulated nitric oxide production through the ETA receptor by suppressing the expression of iNOS and GTP:CHI mRNA in rat mesangial cells.

Pharmacogenetics and polymorphism of human P-450 which activates and detoxicates xenobiotics and carcinogens.

Stereoselective hydroxylation of mephenytoin is expressed polymorphically in the Japanese population: the occurrence of the poor metabolizer was approximately 20% in Japanese, which was 5 to 8 times higher than that in Caucasians. Microsomal 4'-hydroxylation of S-mephenytoin, but not of R-mephenytoin, was correlated to the content of cytochrome P-450 human-2. P-450 human-2 cDNA was cloned and expressed in yeast cells. The expressed P-450 showed stereoselectivities similar to those in human livers for hydroxylations of mephenytoin and hexobarbital enantiomers. The P-450 catalyzed benzo[a]pyrene and tolbutamide hydroxylations and cyclophosphamide oxidation, but showed low activity for the mutagenic activation of IQ (2-amino-3-methylimidazo [4, 5-f]quinoline). Two cDNAs (MP-8 and lambda hPA6), which are two amino acids mutated and deleted, respectively, from P-450 human-2 cDNA were expressed in yeasts. These two expressed P-450s revealed complete loss of the stereoselectivity in the hydroxylation of mephenytoin and hexobarbital. These results indicate that many xenobiotics and carcinogens are detoxicated and activated by the human liver in quite different manners among individuals by reason of genetic differences.