Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Requirement of argininosuccinate lyase for systemic nitric oxide production.

Nature medicine | Nov 13, 2011

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.

Pubmed ID: 22081021 RIS Download

Mesh terms: Animals | Arginine | Argininosuccinate Lyase | Argininosuccinate Synthase | Argininosuccinic Aciduria | Cell Line | Disease Models, Animal | Endothelial Cells | Female | Fibroblasts | Gene Knockdown Techniques | Humans | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Nitric Oxide | Nitric Oxide Synthase | Nitrites | RNA, Small Interfering | Sequence Analysis, DNA | Swine

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCRR NIH HHS, Id: K01 RR000188
  • Agency: NIGMS NIH HHS, Id: R01 GM090310
  • Agency: NIGMS NIH HHS, Id: T32 GM007526
  • Agency: NIGMS NIH HHS, Id: GM90310
  • Agency: NCRR NIH HHS, Id: M01 RR000188
  • Agency: NICHD NIH HHS, Id: U54 HD061221
  • Agency: NHLBI NIH HHS, Id: R01 HL075511
  • Agency: NIDDK NIH HHS, Id: R01 DK054450
  • Agency: NIDDK NIH HHS, Id: DK081735
  • Agency: NCRR NIH HHS, Id: RR00188
  • Agency: NIDDK NIH HHS, Id: R01 DK037175
  • Agency: Canadian Institutes of Health Research, Id: R01 HL022512
  • Agency: NHLBI NIH HHS, Id: R01 HL022512-34
  • Agency: NHLBI NIH HHS, Id: GM07526
  • Agency: NIGMS NIH HHS, Id: RR19453
  • Agency: NCRR NIH HHS, Id: RR024173
  • Agency: NCRR NIH HHS, Id: U54 RR019453
  • Agency: NCRR NIH HHS, Id: K08 DK081735
  • Agency: NIDDK NIH HHS, Id: DK37175
  • Agency: NIDDK NIH HHS, Id: HL75511
  • Agency: NHLBI NIH HHS, Id: R37 DK037175
  • Agency: NIDDK NIH HHS, Id: DK54450
  • Agency: NIDDK NIH HHS, Id: K01 RR024173
  • Agency: NCRR NIH HHS, Id:

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.