RGD Reference Report - Proteomic analysis reveals alterations in the renal kallikrein pathway during hypoxia-induced hypertension. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Proteomic analysis reveals alterations in the renal kallikrein pathway during hypoxia-induced hypertension.

Authors: Thongboonkerd, V  Gozal, E  Sachleben LR, JR  Arthur, JM  Pierce, WM  Cai, J  Chao, J  Bader, M  Pesquero, JB  Gozal, D  Klein, JB 
Citation: Thongboonkerd V, etal., J Biol Chem. 2002 Sep 20;277(38):34708-16. Epub 2002 Jul 16.
RGD ID: 1643146
Pubmed: PMID:12121987   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M203799200   (Journal Full-text)

Obstructive sleep apnea syndrome (OSAS), a disorder characterized by episodic hypoxia (EH) during sleep, is associated with systemic hypertension. We used proteomic analysis to examine differences in rat kidney protein expression during EH, and their potential relationship to EH-induced hypertension. Young male Sprague-Dawley rats were exposed to either EH or sustained hypoxia (SH) for 14 (EH14/SH14) and 30 (EH30/SH30) days. Mean arterial blood pressure was significantly increased only in EH30 (p < 0.0002). Kidney proteins were resolved by two-dimensional-PAGE and were identified by MALDI-MS. Renal expression of kallistatin, a potent vasodilator, was down-regulated in all animals. Expression of alpha-1-antitrypsin, an inhibitor of kallikrein activation, was up-regulated in EH but down-regulated in SH. Western blotting showed significant elevation of B(2)-bradykinin receptor expression in all normotensive animals but remained unchanged in hypertensive animals. Proteins relevant to vascular hypertrophy, such as smooth muscle myosin and protein-disulfide isomerase were up-regulated in EH30 but were down-regulated in SH30. These data indicate that EH induces changes in renal protein expression consistent with impairment of vasodilation mediated by the kallikrein-kallistatin pathway and vascular hypertrophy. In contrast, SH-induced changes suggest the kallikrein- and bradykinin-mediated compensatory mechanisms for prevention of hypertension and vascular remodeling. To test the hypothesis suggested by the proteomic data, we measured the effect of EH on blood pressure in transgenic hKLK1 rats that overexpress human kallikrein. Transgenic hKLK1 animals were protected from EH-induced hypertension. We conclude that EH-induced hypertension may result, at least in part, from altered regulation of the renal kallikrein system.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to hypoxia  IEP 1643146 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpina1  (serpin family A member 1)


Additional Information