Department of Pharmacology, Physiology and Neuroscience, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, Newark, New Jersey 07103, United States.
Published: November 2020
AI Article Synopsis
Article Abstract
Cationic amino acid transporters (CATs) supply cells with essential and semiessential dibasic amino acids. Among them, l-arginine is the substrate for nitric oxide synthases (NOS) to produce nitric oxide (NO), a key signaling molecule and second messenger. In cardiac preparations, we showed that NO acutely and directly modulates transport activity by noncompetitively inhibiting these CATs. We hypothesize that this NO regulation occurs through modification of cysteine residues in CAT proteins. Homology modeling and a computational chemistry approach identified Cys as one of two putative targets for NO binding, of 15 Cys residues present in the low-affinity mouse CAT-2A (mCAT-2A). To test this prediction, mammalian cell lines overexpressing mCAT-2A were used for site-directed mutagenesis and uptake studies. When Cys was replaced with alanine (CysAla), mCAT-2A became insensitive to inhibition by NO donors. In addition, the transport capacity of this variant decreased by >50% compared to that of the control, without affecting membrane expression levels or apparent affinities for the transported amino acids. Interestingly, replacing Cys with serine (CysSer) restored uptake levels to those of the control while retaining NO insensitivity. Other Cys residues, when replaced with Ala, still produced a NO-sensitive CAT-2A. In cells co-expressing NOS and mCAT-2A, exposure to extracellular l-arginine inhibited the uptake activity of control mCAT-2A, via NO production, but not that of the CysSer variant. Thus, the -SH moiety of Cys is largely responsible for mCAT-2A inhibition by NO. Because of the endogenous NO effect, this modulation is likely to be physiologically relevant and a potential intervention point for therapeutics.
This Letter describes the first, to the best of our knowledge, demonstration of a velocity measurement by nitric oxide ionization induced flow tagging and imaging (NiiFTI) of a high-enthalpy hypersonic flow utilizing naturally formed nitric oxide. The measurements were conducted in the hypervelocity expansion tunnel (HXT) at Texas A&M University in Mach 8.5 and Mach 10 flows near an ogive test article.
Cold stress is an environmental factor that seriously restricts the growth, production and survival of plants, and has received extensive attention in recent years. Hydrogen sulfide (HS) is an ubiquitous gas signaling molecule, and its role in alleviating plant cold stress has become a research focus in recent years. This paper reviews for the first time the significant effect of HS on improving plant cold resistance, which makes up for the gaps in the existing literature.
Introduction: Epilepsy remains a challenge, with one-third of patients experiencing refractory seizures despite current anti-seizure medications. The nitrergic system, which involves nitric oxide (NO) and NO synthase (NOS) enzymes, plays a complex role in seizure pathophysiology. Pentoxifylline (PTPh), an FDA-approved phosphodiesterase inhibitor, has anticonvulsant effects; however, its relationship with the pathway is unclear.
Middle Eastern countries, such as the United Arab Emirates and Oman, are affected by frequent dust storms and extreme hot climatic conditions, which can exacerbate respiratory conditions. These environmental factors are particularly injurious to asthmatic patients, as they can aggravate small airway disease (SAD), leading to increased morbidity and healthcare challenges. The evaluation of maximal mid-expiratory flow (MEF-25) as a diagnostic and therapeutic tool for early-stage small airway dysfunction is of significant clinical importance, particularly in hot and arid metropolitan environments where dusty conditions exacerbate pulmonary issues.
