ABSTRACT
Background The redox-sensitive chaperone DJ -1 and uncoupling protein 2 are protective against mitochondrial oxidative stress. We previously reported that renal-selective depletion and germline deletion of DJ -1 increases blood pressure in mice. This study aimed to determine the mechanisms involved in the oxidative stress-mediated hypertension in DJ -1 -/- mice. Methods and Results There were no differences in sodium excretion, renal renin expression, renal NADPH oxidase activity, and serum creatinine levels between DJ -1 -/- and wild-type mice. Renal expression of nitro-tyrosine, malondialdehyde, and urinary kidney injury marker-1 were increased in DJ -1 -/- mice relative to wild-type littermates. mRNA expression of mitochondrial heat shock protein 60 was also elevated in kidneys from DJ -1 -/- mice, indicating the presence of oxidative stress. Tempol-treated DJ -1 -/- mice presented higher serum nitrite/nitrate levels than vehicle-treated DJ -1 -/- mice, suggesting a role of the NO system in the high blood pressure of this model. Tempol treatment normalized renal kidney injury marker-1 and malondialdehyde expression as well as blood pressure in DJ -1 -/- mice, but had no effect in wild-type mice. The renal Ucp2 mRNA expression was increased in DJ -1 -/- mice versus wild-type and was also normalized by tempol. The renal-selective silencing of Ucp2 led to normalization of blood pressure and serum nitrite/nitrate ratio in DJ -1 -/- mice. Conclusions The deletion of DJ -1 leads to oxidative stress-induced hypertension associated with downregulation of NO function, and overexpression of Ucp2 in the kidney increases blood pressure in DJ -1 -/- mice. To our knowledge, this is the first report providing evidence of the role of uncoupling protein 2 in blood pressure regulation.
