Angiotensin II-Induced Mesangial Cell Apoptosis: Role of Oxidative Stress

Lodha, Saurabh; Dani, Dhimant; Mehta, Rajeev; Bhaskaran, Madhu; Reddy, Krishna; Ding, Guohua; Singhal, Pravin C.

doi:10.1007/bf03402088

Cited by 83 publications

(61 citation statements)

References 53 publications

(67 reference statements)

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“…Likewise, systemic propranolol, a beta blocker, has also shown efficacy in hemangiomas of infancy (18). Propranolol has activity against reactive oxygen in addition to its activity against the β-adrenergic receptor (19).…”

Section: Discussionmentioning

confidence: 99%

Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice

et al. 2009

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Hemangiomas are the most common type of tumor in infants. As they are endothelial cell-derived neoplasias, their growth can be regulated by the autocrine-acting Tie2 ligand angiopoietin 2 (Ang2). Using an experimental model of human hemangiomas, in which polyoma middle T-transformed brain endothelial (bEnd) cells are grafted subcutaneously into nude mice, we compared hemangioma growth originating from bEnd cells derived from wild-type, Ang2 +/-, and Ang2 -/-mice. Surprisingly, Ang2-deficient bEnd cells formed endothelial tumors that grew rapidly and were devoid of the typical cavernous architecture of slow-growing Ang2-expressing hemangiomas, while Ang2 +/-cells were greatly impaired in their in vivo growth. Gene array analysis identified a strong downregulation of NADPH oxidase 4 (Nox4) in Ang2 +/-cells. Correspondingly, lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreased Ang2 mRNA levels and greatly impaired hemangioma growth in vivo. Using a structure-based approach, we identified fulvenes as what we believe to be a novel class of Nox inhibitors. We therefore produced and began the initial characterization of fulvenes as potential Nox inhibitors, finding that fulvene-5 efficiently inhibited Nox activity in vitro and potently inhibited hemangioma growth in vivo. In conclusion, the present study establishes Nox4 as a critical regulator of hemangioma growth and identifies fulvenes as a potential class of candidate inhibitor to therapeutically interfere with Nox function.

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Section: Discussionmentioning

confidence: 99%

Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice

et al. 2009

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“…To confirm the effect of morphine on RGEC apoptosis, RGECs treated under control and experimental conditions were assayed by the TdT-mediated dUTP nick end labeling method (kit supplied by Roche Applied Science, Indianapolis, IN) (28).…”

Section: ϫ6mentioning

confidence: 99%

Role of oxidative stress and heme oxygenase activity in morphine-induced glomerular epithelial cell growth

Patel

Manjappa

Bhat

et al. 2003

American Journal of Physiology-Renal Physiology

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Opiate addiction has been reported to contribute to the progression of renal injury. In addition, opiate addiction is a major risk factor for the development of human immunodeficiency virus-associated nephropathy. In the present study, we evaluated the effects of morphine, an active metabolite of heroin, on glomerular epithelial cell (GEC) growth and the involved molecular mechanism. At lower concentrations, morphine promoted GEC proliferation; however, at higher concentrations, morphine triggered apoptosis. Antioxidants inhibited morphine-induced proliferation as well as apoptosis. Similarly, free radical scavengers prevented morphine-induced GEC proliferation and apoptosis. Because proliferative and proapoptotic effects of morphine were inhibited by free radical scavengers as well as antioxidants, it appears that these effects of morphine are mediated through oxidative stress. Hemin, an inducer of heme oxygenase (HO) activity, inhibited GEC proliferation and promoted GEC apoptosis under basal and morphine-stimulated conditions. On the other hand, zinc protoporphyrin, an inhibitor of HO activity, promoted GEC proliferation and inhibited GEC apoptosis under basal as well as morphine-stimulated conditions. These findings suggest that HO activity is directly related to GEC apoptosis and inversely related to GEC proliferation. Morphine, de novo, had bimodal effects on HO activity: lower concentrations increased and higher concentrations decreased HO activity. It appears that HO activity may be modifying morphine-induced GEC growth.

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“…Mesangial cell apoptosis [174] and cellular hypertrophy, respectively, due to MAP kinase and ERK1/ERK2 pathways [175], explain the development of epithelial-mesenchymal transition (EMT) [176,177] caused by NOX-derived ROS. EMT of tubular epithelial cells is characterized by loss of epithelial properties and gain of excessive deposition of extracellular matrixproducing characteristics of myofibroblast [178,179].…”

Section: Kidney and Oxidative Stressmentioning

confidence: 99%

Free Radicals and Biomarkers Related to the Diagnosis of Cardiorenal Syndrome

Restini¹,

Pereira²,

Geleilete³

2016

Free Radicals and Diseases

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The National Heart, Lung, and Blood Institute Working Group has postulated the cardiorenal syndrome (CRS) as an interaction between the kidneys and the cardiovascular system in which therapy to relieve congestive heart failure (HF) symptoms is limited by the further worsening renal function. CRS is classified from type I to V, taking into account the progression of the symptoms in terms of mechanisms, clinical conditions, and biomarkers. Experimental and clinical studies have shown the kidney as both a trigger and a target to sympathetic nervous system (SNS) overactivity. Renal damage and ischemia, activation of the renin angiotensin aldosterone system (RAAS), and dysfunction of nitric oxide (NO) system are associated with kidney adrenergic activation. Indeed, the imbalances of RAAS and/or SNS share an important common process in CRS: the activation and production of free radicals, especially reactive oxygen species (ROS). The present chapter addresses connections of the free radicals as potential biomarkers as the imbalances in the RAAS and the SNS are developed. Understanding the involvement of free radicals in CRS may bring knowledge to design studies in order to develop accurate pharmacological interventions.

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Angiotensin II-Induced Mesangial Cell Apoptosis: Role of Oxidative Stress

Cited by 83 publications

References 53 publications

Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice

Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice

Role of oxidative stress and heme oxygenase activity in morphine-induced glomerular epithelial cell growth

Free Radicals and Biomarkers Related to the Diagnosis of Cardiorenal Syndrome

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