Protein carbonylation in kidney medulla of the spontaneously hypertensive rat

Abstract

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.

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

“…The medulla is an area that is significant in determining the level at which blood pressure may be set (7) and is a relatively hypoxic area and under oxidative stress (1). This is exacerbated in hypertension as demonstrated in recent proteomic studies in the medulla of the spontaneously hypertensive rat where there was enhanced nitration of proteins involved in NO signaling and antioxidant defense (22) as well as raised carbonylation of enolase 1 and catalase (23). Lenda and Boegehold (14) reported that exposure of rats to a high-salt diet resulted in a raised oxidant activity within the walls of arterioles in the skeletal microvasculature which they attributed to increased NAD(P)H oxidase activity (15).…”

Mitochondrial proteomic analysis reveals deficiencies in oxygen utilization in medullary thick ascending limb of Henle in the Dahl salt-sensitive rat

“…These investigators suggested that the sulfenated and carbonylated proteins could be targets of enhanced ROS generation with ROS acting as a signaling molecule and not as the direct inducer of oxidative damage. Some of the proteins identified by Tyther et al (76,77) are known to be redox sensitive and importantly involved in metabolism, antioxidant defense, and regulation of nitric oxidase synthase. However, only six out of 53 of the sulfenated proteins and four out of 12 of the carbonylated proteins were mitochondrial, none of which were differently expressed in the present mTAL study.…”

“…A proteomic analysis of whole medullary tissue by Tyther et al showed that protein sulfenation (76) and protein carbonylation (77) were enhanced in the renal medulla of SHR rats compared with normotensive Wistar rats. These investigators suggested that the sulfenated and carbonylated proteins could be targets of enhanced ROS generation with ROS acting as a signaling molecule and not as the direct inducer of oxidative damage.…”

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

“…In a large cohort of Chinese adults, plasma reactive carbonyl species was positively associated with blood pressure levels and was found to be an important risk factor for developing hypertension (36). Nitration of proteins, especially modification of tyrosine to 3-nitrotyrosine, is another form of redox modification and is increased in serum proteins in patients with hypertension, chronic kidney disease, and diabetes (25,131,217).…”