NADPH Oxidase 4 Induces Cardiac Arrhythmic Phenotype in Zebrafish
JOURNAL OF BIOLOGICAL CHEMISTRY
Authors: Zhang, Yixuan; Shimizu, Hirohito; Siu, Kin Lung; Mahajan, Aman; Chen, Jau-Nian; Cai, Hua
Abstract
Oxidative stress has been implicated in cardiac arrhythmia, although a causal relationship remains undefined. We have recently demonstrated a marked up-regulation of NADPH oxidase isoform 4 (NOX4) in patients with atrial fibrillation, which is accompanied by overproduction of reactive oxygen species (ROS). In this study, we investigated the impact on the cardiac phenotype of NOX4 overexpression in zebrafish. One-cell stage embryos were injected with NOX4 RNA prior to video recording of a GFP-labeled (myl7:GFP zebrafish line) beating heart in real time at 24-31 h post-fertilization. Intriguingly, NOX4 embryos developed cardiac arrhythmia that is characterized by irregular heartbeats. When quantitatively analyzed by an established LQ-1 program, the NOX4 embryos displayed much more variable beat-to-beat intervals (mean S. D. of beat-to-beat intervals was 0.027 s/beat in control embryos versus 0.038 s/beat in NOX4 embryos). Both the phenotype and the increased ROS in NOX4 embryos were attenuated by NOX4 morpholino co-injection, treatments of the embryos with polyethylene glycol-conjugated superoxide dismutase, or NOX4 inhibitors fulvene-5, 6-dimethylaminofulvene, and proton sponge blue. Injection of NOX4-P437H mutant RNA had no effect on the cardiac phenotype or ROS production. In addition, phosphorylation of calcium/calmodulin- dependent protein kinase II was increased in NOX4 embryos but diminished by polyethylene glycol-conjugated superoxide dismutase, whereas its inhibitor KN93 or AIP abolished the arrhythmic phenotype. Taken together, our data for the first time uncover a novel pathway that underlies the development of cardiac arrhythmia, namely NOX4 activation, subsequent NOX4-specific NADPH-driven ROS production, and redox-sensitive CaMKII activation. These find-ings may ultimately lead to novel therapeutics targeting cardiac arrhythmia.
Line x tester analysis across equatorial environments to study combining ability of Indonesian maize inbred
ASIAN JOURNAL OF AGRICULTURE AND BIOLOGY
Authors: Andayani, N. N.; Aqil, M.; Efendi, Roy; Azrai, M.
Abstract
Selection of optimal combination in hybrid development is crucial to successful breeding program and key determining factor for generating superior variety. Knowledge of gene combination system of maize traits under equatorial environments has not been extensively studied. It is the aim of this study to assess the performance of maize inbred lines across equatorial environments in Indonesia. Twelve test crosses (MAL01 x MYL10, MR14 x MYL10, MAL01 x MYL12, MR14 x MYL12, MAL01 x MYL15, MR14 x MYL15, MAL01 x MYL16, MR14 x MYL16, MAL01 x MYL2, MR14 x MYL2, MAL01 x MYL7 and MR14 x MYL7) and three commercial hybrids (NK 33, DK979 and Bima 11) were investigated for six agronomic components in randomized complete block design across six locations in Indonesia. The results revealed that interaction of crosses versus environment was significant for grain yield, maturity and other agronomic components. The estimates of GCA exhibited that lines MYL10 (L3), MYL15 (L5) and tester MR14 (T2) were a good general combiner, hence MYL10 (L3), MYL15 (L5) and tester MR14 (T2) can be used for generating superior maize hybrid. Combined analysis of SCA effects showed that the crosses MYL 10 (L3) x MR 14 (T2) gave the highest yield of 10.73 t/ha and significantly superior to the best check DK979 (10.17). The hybrid from this cross has to be evaluated in advance to determine the prospect for release as a new commercial hybrid in Indonesia.