Proteomics Research Group, Department of Biochemistry, University College Cork, Ireland.
Department of Physiology, University College Cork, Ireland.
Proteomics Clin Appl. 2009 Mar;3(3):338-46. doi: 10.1002/prca.200780098. Epub 2009 Feb 13.
Enhanced generation of ROS has been reported in models of hypertension such as the spontaneously hypertensive rat (SHR). Impairment of kidney function has been implicated in development and progression of hypertension, and the renal medulla appears to play an important role in regulating long-term blood pressure. A key biomarker of oxidative stress is the formation of protein carbonyls, which we set out to characterize in the SHR medulla. We identified 11 proteins that were differentially carbonylated in SHR medulla in comparison to normotensive wistars including enolase 1, catalase, carbonic anhydrase II, transferrin and members of the aldo-keto-reductase family. This enhanced protein oxidation was not only accompanied by an increase in intracellular iron deposition, but aldo-keto-reductase activity was also significantly less in SHR medulla than in normotensive Wistars. Oxidative stress appears selectively to target a subset of proteins in SHR kidney and modification of these proteins may in turn contribute to the renopathy associated with hypertension.
已经有研究报道,在自发性高血压大鼠(SHR)等高血压模型中,活性氧(ROS)的生成增强。肾功能损害与高血压的发生和发展有关,而肾脏髓质似乎在调节长期血压方面发挥着重要作用。氧化应激的一个关键生物标志物是蛋白质羰基的形成,我们着手研究 SHR 髓质中的这种羰基。与正常血压的 Wistar 大鼠相比,我们在 SHR 髓质中发现了 11 种差异羰基化的蛋白质,包括烯醇酶 1、过氧化氢酶、碳酸酐酶 II、转铁蛋白和醛酮还原酶家族成员。这种增强的蛋白质氧化不仅伴随着细胞内铁沉积的增加,而且 SHR 髓质中的醛酮还原酶活性也明显低于正常血压的 Wistar 大鼠。氧化应激似乎选择性地针对 SHR 肾脏中的一组特定蛋白质,这些蛋白质的修饰可能反过来导致与高血压相关的肾病变。