Calcium channel blocker, azelnidipine, reduces lipid hydroperoxides in patients with type 2 diabetes independent of blood pressure.
(41/140)Anti-hypertensive agents with antioxidative effects are potentially useful for diabetic patients with hypertension to prevent the onset and progression of their complication. While dihydropyridine-type calcium antagonists are among the frequently used anti-hypertensive drugs, azelnidipine, a novel calcium antagonist, has been reported to have a unique anti-oxidative effect in vitro and in animals. In this study, we measured lipid hydroperoxides in human sample using diphenyl-1-pyrenylphosphine for the first time, and used the value of lipid hydroperoxides as an index of oxidative stress. Then, we compared the antioxidative properties of azelnidipine and amlodipine, a frequently used calcium antagonist in hypertensive diabetic patients. Administration of vitamin C and E for 8 weeks significantly reduced lipid hydroperoxides in erythrocyte membrane in normal subjects. In hypertensive diabetic patients, azelnidipine treatment for 12 weeks induced a more significant fall in erythrocyte lipid hydroperoxide level than amlodipine, though blood pressure during each treatment was comparable. Our data confirm the usefulness of lipid hydroperoxides in erythrocyte membrane as a marker of oxidative stress in vivo, and indicate that azelnidipine has a unique antioxidative property in human. (+info)
Nicotianamine preferentially inhibits Angiotensin I-converting enzyme.
(42/140)Nicotianamine (NA) is a nonprotein amino acid that inhibits the angiotensin I-converting enzyme (ACE) in the renin-angiotensin system (RAS). The purpose of this study is to prove that NA contributes to the suppression of hypertension by preferential inhibition of ACE. On comparison with EDTA-a chelator-we found that the inhibition pattern of NA for ACE is that of mixed inhibition and that NA exhibits weak chelation effects for zinc, copper, and cobalt ions. Therefore, we investigated whether NA inhibited zinc-containing enzymes other than ACE in vitro. The results revealed that NA does not inhibit leucine aminopeptidase or alkaline phosphatase in rat serum. On the other hand, NA demonstrated specific inhibitory effects for rat serum ACE and aortic ACE. These results suggest that the preferential inhibition of circulatory and tissue ACE by NA can contribute to the suppression of hypertension. (+info)
Mutation in nicotianamine aminotransferase stimulated the Fe(II) acquisition system and led to iron accumulation in rice.
(43/140)Higher plants acquire iron (Fe) from the rhizosphere through two strategies. Strategy II, employed by graminaceous plants, involves secretion of phytosiderophores (e.g. deoxymugineic acid in rice [Oryza sativa]) by roots to solubilize Fe(III) in soil. In addition to taking up Fe in the form of Fe(III)-phytosiderophore, rice also possesses the strategy I-like system that may absorb Fe(II) directly. Through mutant screening, we isolated a rice mutant that could not grow with Fe(III)-citrate as the sole Fe source, but was able to grow when Fe(II)-EDTA was supplied. Surprisingly, the mutant accumulated more Fe and other divalent metals in roots and shoots than the wild type when both were supplied with EDTA-Fe(II) or grown under water-logged field conditions. Furthermore, the mutant had a significantly higher concentration of Fe in both unpolished and polished grains than the wild type. Using the map-based cloning method, we identified a point mutation in a gene encoding nicotianamine aminotransferase (NAAT1), which was responsible for the mutant phenotype. Because of the loss of function of NAAT1, the mutant failed to produce deoxymugineic acid and could not absorb Fe(III) efficiently. In contrast, nicotianamine, the substrate for NAAT1, accumulated markedly in roots and shoots of the mutant. Microarray analysis showed that the expression of a number of the genes involved in Fe(II) acquisition was greatly stimulated in the naat1 mutant. Our results demonstrate that disruption of deoxymugineic acid biosynthesis can stimulate Fe(II) acquisition and increase iron accumulation in rice. (+info)
Deoxymugineic acid increases Zn translocation in Zn-deficient rice plants.
Distribution of L-azetidine-2-carboxylate N-acetyltransferase in yeast.
(45/140)The budding yeast Saccharomyces cerevisiae Sigma1278b contains the MPR1 gene encoding N-acetyltransferase, which detoxifies the L-proline analog L-azetidine-2-carboxylate (AZC). Of 131 yeasts tested, AZC acetyltransferase activity was detected in 17 strains of 41 strains that showed AZC resistance. Degenerate-PCR analysis revealed that two strains, i.e., Candida saitoana AKU4533 and Wickerhamia fluorescens AKU4722, contained a DNA fragment highly homologous to MPR1. This indicates that AZC acetyltransferases are widely distributed in yeasts. (+info)
GTPase-mediated regulation of the unfolded protein response in Caenorhabditis elegans is dependent on the AAA+ ATPase CDC-48.
Genes and enzymes of azetidine-2-carboxylate metabolism: detoxification and assimilation of an antibiotic.
Effects of azelnidipine on the autonomic functions and its influence on arterial stiffness and endothelial functions.