Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice

Godin, Nicolas; Liu, Fang; Lau, Garnet; Brezniceanu, Marie-Luise; Chénier, Isabelle; Filep, János G.; Ingelfinger, Julie R.; Zhang, Shaoling; Chan, John S.D.

doi:10.1038/ki.2010.63

Cited by 83 publications

(116 citation statements)

References 45 publications

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“…In angiotensinogen-overexpresing mice, which are hypertensive, catalase overexpression prevented blood pressure elevation and protected against kidney damage (68). In human studies, plasma vitamin C levels are inversely related to blood pressure levels, indicating a potential blood pressure-lowering effect of this antioxidant (94).…”

Section: Antioxidant Defense Mechanismsmentioning

confidence: 94%

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

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

236

177

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Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

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Section: Antioxidant Defense Mechanismsmentioning

confidence: 94%

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

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

236

177

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“…Furthermore, in double Tg mice having Agt and CAT specifically expressed in their RPTCs, ROS generation, NADPH activity and levels of hemoxygenase 1 (HO-1) were significantly lowered by CAT overactivity compared to Agt-Tg mice. Levels of collagen type IV, monocyte chemotactic protein-1 (MCP-1), TGF- 1 and plasminogen activator inhibitor-1 were also lowered by CAT overexpression in double Tg mice compared to Agt Tg mice (37). Thus, CAT overexpression alleviates oxidative stress in RPTC and reduces the toxicity of Ang II and chronic hyperglycemia on the kidneys.…”

Section: Diabetic Nephropathy 36mentioning

confidence: 73%

Renal Angiotensinogen Gene Expression and Tubular Atrophy in Diabetic Nephropathy

Nouthe¹,

Saleh²,

Zhang³

et al. 2012

Diabetic Nephropathy

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“…Indeed, the antioxidative action of catalase on PTCs has been reported to attenuate AngII-induced hypertension. 25 AngII increases generation of hydrophobic ROS, such as superoxide anion (O 2 − ) and hydrogen peroxide via the action of nicotinamide adenine dinucleotide phosphate oxidase. 23 The antioxidant activity of L-FABP is thought to result from the inactivation of free radicals by methionine and cysteine amino acids in L-FABP and also by exposure of the L-FABP-binding site to lipid peroxides, 26 indicating that L-FABP has both hydrophilic and lipophilic antioxidant effects.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Angiotensin II–Induced Salt-Sensitive Hypertension by Liver-Type Fatty Acid–Binding Protein in Proximal Tubules

Osaki

Suzuki²,

Sugaya³

et al. 2013

Hypertension

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Abstract-Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT.Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT. 14 The expression of renal hL-FABP is upregulated in the pathological conditions in these mice, with tubulointerstitial inflammation and fibrosis being markedly attenuated compared with wild-type (WT) mice.12,14 However, the pathophysiological significance of tubular hL-FABP in local RAS activation and subsequent SSHT remains to be determined. The present study analyzed AngII-induced SSHT in hL-FABPTg mice and investigated the underlying mechanism in PTCs with or without hL-FABP transfection or treatment of recombinant L-FABP peptides (rhL-FABP). MethodsA detailed description of all methods is presented in the online-only Data Supplement. Results AngII-Induced SSHT Was Prevented in hL-FABPTg MiceAll groups had the same level of systolic blood pressure (SBP; 102-112 mm Hg) at the beginning of the study (Figure 1). AngII infusion in the WT mice induced a progressive increase in SBP (159.1±13.7 and 177.2±10.7 mm Hg at weeks 2 and 4, respectively; P<0.001 versus WT before and AngII hL-FABPTg at week 4; Figure 1). However, AngII infusion in hL-FABPTg mice induced a small incre...

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Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice

Cited by 83 publications

References 45 publications

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

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

Renal Angiotensinogen Gene Expression and Tubular Atrophy in Diabetic Nephropathy

Amelioration of Angiotensin II–Induced Salt-Sensitive Hypertension by Liver-Type Fatty Acid–Binding Protein in Proximal Tubules

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