Uncoupling Protein 2 Increases Blood Pressure in DJ-1 Knockout Mice

Academic Article

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.
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    Author List

  • De Miguel C; Hamrick WC; Sedaka R; Jagarlamudi S; Asico LD; Jose PA; Cuevas S
  • Volume

  • 8
  • Issue

  • 9