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

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dc.contributor.authorThongboonkerd, V
dc.contributor.authorGozal, E.
dc.contributor.authorSachleben, L. R.
dc.contributor.authorArthur, J. M.
dc.contributor.authorPierce, W. M.
dc.contributor.authorCai, J.
dc.contributor.authorChao, J.
dc.contributor.authorBader, M.
dc.contributor.authorPesquero, João Bosco [UNIFESP]
dc.contributor.authorGozal, D.
dc.contributor.authorKlein, J. B.
dc.contributor.institutionUniv Louisville
dc.contributor.institutionMax Delbruck Ctr Mol Med
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionMed Univ S Carolina
dc.contributor.institutionVet Adm Med Ctr
dc.date.accessioned2016-01-24T12:33:31Z
dc.date.available2016-01-24T12:33:31Z
dc.date.issued2002-09-20
dc.description.abstractObstructive 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.en
dc.description.affiliationUniv Louisville, Kidney Dis Program, Core Proteom Lab, Dept Med, Louisville, KY 40202 USA
dc.description.affiliationUniv Louisville, Dept Pediat, Kosair Childrens Hosp Res Inst, Louisville, KY 40202 USA
dc.description.affiliationUniv Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40202 USA
dc.description.affiliationUniv Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA
dc.description.affiliationMax Delbruck Ctr Mol Med, Berlin, Germany
dc.description.affiliationEscola Paulista Med, Dept Biophys, São Paulo, Brazil
dc.description.affiliationMed Univ S Carolina, Dept Med, Charleston, SC 29425 USA
dc.description.affiliationMed Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
dc.description.affiliationVet Adm Med Ctr, Louisville, KY 40202 USA
dc.description.affiliationUnifespEscola Paulista Med, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent34708-34716
dc.identifierhttp://dx.doi.org/10.1074/jbc.M203799200
dc.identifier.citationJournal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 277, n. 38, p. 34708-34716, 2002.
dc.identifier.doi10.1074/jbc.M203799200
dc.identifier.issn0021-9258
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/26982
dc.identifier.wosWOS:000178117000009
dc.language.isoeng
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleProteomic analysis reveals alterations in the renal kallikrein pathway during hypoxia-induced hypertensionen
dc.typeinfo:eu-repo/semantics/article
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