Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

Aminzadeh, Mohammad A.; Satô, Tadashi; Vaziri, Nosratola D.

doi:10.1016/j.trsl.2012.03.003

Cited by 17 publications

(16 citation statements)

References 47 publications

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“…In confirmation of earlier studies [8,9,14,30] oxidative stress and inflammation in the remnant kidney tissues in the vehicle-treated CKD rats were accompanied by impaired Nrf2 activity and downregulation of its target gene products. Long-term treatment with dh404 at 2 mg/kg/day restored Nrf2 activity and expression of its target gene products.…”

Section: Discussionsupporting

confidence: 88%

“…ROS production is markedly increased in the diseased kidney, as well as vascular and various other tissues. This is primarily driven by activation or upregulation of the ROS-producing enzymes (NAD(P)H oxidase (NOX) isoforms, cycloxygenase-2, lipoxygenase, and uncoupled nitric oxide synthase), mitochondrial dysfunction, and endoplasmic reticulum stress [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Vaziri¹,

Liu²,

Farzaneh³

et al. 2015

Free Radical Biology and Medicine

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Oxidative stress and inflammation play a central role in progression and complications of CKD and are, in part, due to impairment of the Nrf2 system which regulates expression of antioxidant and detoxifying molecules. Natural Nrf2 inducing phytochemicals have been shown to ameliorate kidney disease in experimental animals. However due to adverse outcomes clinical trial of synthetic Nrf2 activator, bardoxolone methyl (BARD), in CKD patients was terminated. BARD activates Nrf2 via 2 covalent modification of reactive cysteine residues in Nrf2 repressor molecule, Keap-1. In addition to Nrf2, Keap1 suppresses IKKB, the positive regulator of NF k B. Treatment with BARD analog, dh404, at 5-20 mg/kg/day in diabetic obese Zucker rats exacerbates whereas its use at 2 mg/kg/day in 5/6 nephrectomized rats attenuates CKD progression. We, therefore, hypothesized that deleterious effects of high dose BARD are mediated by activation of NF k B.CKD (5/6 nephrectomized) rats were randomized to receive dh404 (2 or 10mg/kg/day) or vehicle for 12 weeks. Vehicle-treated group exhibited glomerulosclerosis, interstitial fibrosis and inflammation, activation of NF k B, upregulation of oxidative, inflammatory and fibrotic pathways, and suppression of Nrf2 activity and its key target gene products. Treatment with low dose dh404 restored Nrf2 activity and expression of its target genes, attenuated activation of NF k B and fibrotic pathways, and reduced glomerulosclerosis, interstitial fibrosis and inflammation. In contrast treatment with high dh404 dosage intensified proteinuria, renal dysfunction and histological abnormalities, amplified up-regulations of NF k B and fibrotic pathways, and suppression of Nrf2 system. Thus therapy with BARD analogs exerts a dose-dependent dimorphic impact on CKD progression.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Vaziri¹,

Liu²,

Farzaneh³

et al. 2015

Free Radical Biology and Medicine

Self Cite

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show abstract

“…The processes of apoptosis and oxidative stress were represented among the 18 proteins confirmed with SRM. The cascade leading from oxidative stress to apoptosis was indirectly linked to RAS in the kidney (54). AngII was previously shown to induce apoptosis in PTECs (55)(56)(57), as well as in other kidney cells (58,59).…”

Section: Discussionmentioning

confidence: 99%

Determination of an Angiotensin II-regulated Proteome in Primary Human Kidney Cells by Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC)

Konvalinka

Zhou

Dimitromanolakis

et al. 2013

Journal of Biological Chemistry

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“…The target proteins in the kidney and colon tissues were measured by western blot analysis as described previously (Eschbach et al, 1987;Kim and Vaziri, 2010;Aminzadeh et al, 2012) using the following antibodies. Rabbit antibodies against rat nuclear factor-κB p65…”

Section: Western Blot Analysesmentioning

confidence: 99%

Phosphate Binder, Ferric Citrate, Attenuates Anemia, Renal Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in 5/6 Nephrectomized CKD Rats

Jing

Nunes

Farzaneh

et al. 2018

J Pharmacol Exp Ther

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Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

Cited by 17 publications

References 47 publications

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Determination of an Angiotensin II-regulated Proteome in Primary Human Kidney Cells by Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC)

Phosphate Binder, Ferric Citrate, Attenuates Anemia, Renal Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in 5/6 Nephrectomized CKD Rats

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