Increased release of nitric oxide in ischemic hearts after exercise in patients with effort angina

AbstractObjectives. The aim of this study was to determine whether the release of nitric oxide (NO) from the ischemic heart increases during exercise in patients with effort angina.Background. Myocardial ischemia increases NO production in the canine heart, but no such increase has been demonstrated in the ischemic human heart.Methods. Fifteen patients with effort angina underwent supine ergometer exercise tests. All patients had severe proximal stenosis (>90%) in the left anterior descending coronary artery. The control group consisted of 17 subjects without coronary artery disease or systemic hemodynamic abnormalities.Results. Neither the lactate extraction ratio (LER) nor the difference in NO concentration between coronary venous and arterial blood (ΔVA[NO]) was affected by exercise in the control subjects. In patients with effort angina, neither variable differed from that in the control group at rest; however, exercise markedly decreased LER and significantly increased ΔVA(NO) (from 4.7 ± 0.3 to 16.5 ± 1.6 μmol/liter, p < 0.001) in the patient group. The extent of decrease in LER was significantly correlated with the extent of increase in ΔVA(NO) in the patients with effort angina (r2= −0.837, p < 0.001).Conclusions. Provocation of myocardial ischemia by exercise stress increases NO production in the hearts of patients with effort angina

MYCBPAP is a central apparatus protein required for centrosome–nuclear envelope docking and sperm tail biogenesis in mice

Wang H., Kobayashi H., Shimada K., et al. MYCBPAP is a central apparatus protein required for centrosome–nuclear envelope docking and sperm tail biogenesis in mice. Journal of Cell Science 137, jcs261962 (2024); https://doi.org/10.1242/jcs.261962.The structure of the sperm flagellar axoneme is highly conserved across species and serves the essential function of generating motility to facilitate the meeting of spermatozoa with the egg. During spermiogenesis, the axoneme elongates from the centrosome, and subsequently the centrosome docks onto the nuclear envelope to continue tail biogenesis. Mycbpap is expressed predominantly in mouse and human testes and conserved in Chlamydomonas as FAP147. A previous cryo-electron microscopy analysis has revealed the localization of FAP147 to the central apparatus of the axoneme. Here, we generated Mycbpap-knockout mice and demonstrated the essential role of Mycbpap in male fertility. Deletion of Mycbpap led to disrupted centrosome–nuclear envelope docking and abnormal flagellar biogenesis. Furthermore, we generated transgenic mice with tagged MYCBPAP, which restored the fertility of Mycbpap-knockout males. Interactome analyses of MYCBPAP using Mycbpap transgenic mice unveiled binding partners of MYCBPAP including central apparatus proteins, such as CFAP65 and CFAP70, which constitute the C2a projection, and centrosome-associated proteins, such as CCP110. These findings provide insights into a MYCBPAP-dependent regulation of the centrosome–nuclear envelope docking and sperm tail biogenesis