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Articles by Asad Mian in JoVE
JoVE Clinical and Translational Medicine
Analytiska tekniker för analys av kväveoxid Bioaktivitet
1Texas Therapeutics Institute, University of Texas Health Science Center at Houston, 2Deptartment of Pediatrics, Baylor College of Medicine
Den endogena produktionen av kväveoxid (NO) reglerar ett stort antal olika biologiska funktioner. Det blir allt tydligare att störningar eller dysreglering av NO baserad signalering är involverad i många mänskliga sjukdomar. Metoder för att kvantifiera relevanta inga metaboliter kan ge nya diagnostiska eller prognostiska biomarkörer för sjukdomar hos människor.
Other articles by Asad Mian on PubMed
Requirement of Argininosuccinate Lyase for Systemic Nitric Oxide Production
Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases.
