title: Uric acid induces oxidative stress via an activation of the renin-angiotensin system in 3T3-L1 adipocytes.
abstract: Hyperuricemia is recently reported involving in various obesity-related cardiovascular disorders, especially hypertension. However, the underlying mechanisms are not completely understood. In the present study, we investigated whether uric acid upregulates renin-angiotensin system (RAS) expression in adipocytes. We also examined whether RAS activation plays a role in uric acid-induced oxidative stress in adipocytes. The adipocytes of different phenotypes were incubated with uric acid for 48 h, respectively. Losartan (10(-4) M) or captopril (10(-4) M) was used to block adipose tissue RAS activation. mRNA expressions of angiotensinogen (AGT), angiotensin-converting enzyme-1 (ACE-1), renin, angiotensin type 1 receptor (AT1R), and angiotensin type 2 receptor (AT2R) were evaluated with real-time PCR. Angiotensin II concentrations in supernatant were measured by ELISA. Intracellular reactive species (ROS) levels were measured by fluorescent probe DCFH-DA, DHR, or NBT assay. The uric acid upregulated both RAS (AGT, ACE1, renin, AT1R, and AT2R) mRNA expressions and angiotensin II protein secretion and caused a significant increase in ROS production in 3T3-L1 adipocytes. These effects could be prevented by RAS inhibitors, either losartan or captopril. RAS activation has been causally implicated in oxidative stress induced by uric acid in 3T3-L1 adipocytes, suggesting a plausible mechanism through which hyperuricemia contributes to the pathogenesis of obesity-related cardiovascular diseases.
authors.affiliation: Department of Endocrinology and Metabolism, Southwest Hospital, Third Military Medical University, No. 30, Gaotanyanzheng Street, Shapingba District, Chongqing, 400038, China.
authors.forename: Jun-xia
authors.initials: JX
authors.lastname: Zhang
authors.forename: Yu-ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Qi-nan
authors.initials: QN
authors.lastname: Wu
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000503:physiopathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014527:Uric Acid / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D017382:Reactive Oxygen Species; D000808:Angiotensinogen; D000804:Angiotensin II; D014527:Uric Acid; D002216:Captopril