Rabbit Anti-Human KYNU Polyclonal Antibody

The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-L-kynurenine, to be further transformed to l-kynurenine. Kynurenine aminotransferase-II (KAT-II), l-kynurenine hydrolase (KYNU), and l-kynurenine 3-monooxygenase (KMO) are key enzymes in the later steps of the KP. Nitroglycerin (NTG) administration serves as both human and animal model of migraine, causing the activation and sensitization in the trigeminal system. A previous study demonstrated a reduction of KAT-II expression following NTG administration in animals. The goal of current tests was to identify the potential modulatory effect of NTG on other metabolizing enzymes of the KP in the caudal trigeminal nucleus (TNC) of rats. Four hours following the intraperitoneal injection of NTG (10 mg/kg), the rats were perfused transcardially and the TNC was extracted for Western blotting. Western blot studies revealed that the expression of TDO2, IDO1, KYNU, and KMO decreased in the TNC. The results demonstrated that NTG is able to downregulate the KP, with a potential influence on the glutamatergic system as well, contributing to the development of trigeminal activation and sensitization in animals.

Background-Genetic studies in mouse and human suggest that kynureninase activity may influence blood pressure and renal function. The gene coding kynureninase (KYNU) is also located on chromosome band 2q14-q23, where a linkage peak for essential hypertension was previously detected in the Chinese Han population. Methods and Results-After having found no association with common polymorphisms, this study aimed to assess the role of 1 rare variant of KYNU, Arg188Gln, and kynureninase activity in relation to hypertension. Thirty-three of 1124 Chinese patients with hypertension were heterozygous for Arg188Gln, whereas only 14 of 1084 normotensive controls were heterozygous for Arg188Gln (188G1n allele frequency, 0.015 versus 0.006; P=0.0075). A genotype-discordant sibling-pair study was performed in another 924 individuals from 213 families, indicating that 188G1n carriers had higher systolic blood pressure (168.29 +/- 24.67 versus 139.00 +/- 12.82 mm Hg, P < 0.001) and diastolic blood pressure (105.50 +/- 14.08 versus 90.75 +/- 11.07 mm Hg, P = 0.001) than did Arg188 homozygous siblings. The Arg188Gln variant was found to be rarer in 2 other ethnic groups (3 heterozygous among 880 hypertensive French whites and 0 of 90 black Africans with hypertension). The kynureninase activity in plasma was correlated with blood pressure in subjects from hypertensive families (P < 0.05). The Kinetic Michaelis constants of 188Gln carriers was lower than that of Arg188 homozygous subjects (0.05 +/- 0.02 versus 0.10 +/- 0.02 mmol/L, P = 0.005). Arg188Gln mutation in vitro also showed less catalytic efficiency than the wild-type KYNU enzyme (maximal reaction velocity/Kinetic Michaelis constant ratio, 0.050 +/- 0.012 versus 0.11 +/- 0.016 mL/min per mg; P = 0.029). Conclusions-The results show that the rare KYNU variant Arg188Gln affects kynureninase activity and are consistent with the hypothesis that this mutation can predispose to essential hypertension. (Circ Cardiovasc Genet. 2011;4:687-694.)