Albumin overload activates intrarenal renin–angiotensin system through protein kinase C and NADPH oxidase-dependent pathway

Cao, Wei; Zhou, Qiu Gen; Nie, Jing; Wang, Guo B; Liu, Youhua; Zhou, Zhan Mei; Hou, Fan Fan

doi:10.1097/hjh.0b013e32834786f0

Cited by 53 publications

(43 citation statements)

References 38 publications

(42 reference statements)

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“…The latter studies clearly support a functional intracellular processing pathway for the generation of ANG II within these cells, as well intracellular receptors that mediate the growth response to ANG II. Preliminary studies in the NRK52E cell line, a well-characterized model of rat epithelial cells, support findings for a nuclear RAS in proximal tubules (11). As shown in Fig.…”

Section: Intracellular Formationsupporting

confidence: 77%

Review:Novel roles of nuclear angiotensin receptors and signaling mechanisms

Gwathmey

Alzayadneh

Pendergrass

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

108

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The renin-angiotensin system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The dysregulation of the RAS is considered a major influence in the development and progression of cardiovascular disease and other pathologies. Indeed, experimental and clinical evidence indicates that blockade of this system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT 1R) antagonists is an effective therapy to attenuate hypertension and diabetic renal injury, and to improve heart failure. Originally defined as a circulating system, multiple tissues express a complete RAS, and compelling evidence now favors an intracellular system involved in cell signaling and function. Within the kidney, intracellular expression of the three predominant ANG receptor subtypes is evident in the nuclear compartment. The ANG type 1 receptor (AT 1R) is coupled to the generation of reactive oxygen species (ROS) through the activation of phosphoinositol-3 kinase (PI3K) and PKC. In contrast, both ANG type 2 (AT 2R) and ANG-(1-7) (AT 7R) receptors stimulate nitric oxide (NO) formation, which may involve nuclear endothelial NO synthase (eNOS). Moreover, blockade of either ACE2-the enzyme that converts ANG II to ANG-(1-7)-or the AT 7 receptor exacerbates the ANG II-ROS response on renal nuclei. Finally, in a model of fetal programmed hypertension, the nuclear ROS response to ANG II is enhanced, while both AT 2 and AT7 stimulation of NO is attenuated, suggesting that an imbalance in the intracellular RAS may contribute to the development of programming events. We conclude that a functional intracellular or nuclear RAS may have important implications in the therapeutic approaches to cardiovascular disease. renin-angiotensin system; angiotensin converting enzyme; ACE2; neprilysin; kidney; nuclei; AT 1 ; AT 2 ; AT 7 , FROM THE EARLY STUDIES OF Tigerstedt and Bergman (101) that described renin activity in the kidney to the characterization of a pressor substance subsequently identified as ANG II by the laboratories of Braun-Menendez (6) (hypertensin) and Page (angiotonin) 50 years later (8), the characterization of the renin-angiotensin system (RAS) within the kidney and other tissues continues unabated to broaden our understanding of the functional aspects of this important hormonal system in blood pressure regulation and cardiovascular pathologies. Coupled with the discoveries of ANG I-converting enzyme (ACE) as the primary enzyme that forms ANG II in the circulation and tissue and the molecular identification of the ANG II type 1 receptor (AT 1 ) that confers the predominant actions of ANG II, the "classical" RAS was regarded as a sequential endocrine system to form ANG II for the maintenance of blood pressure through renal, vascular, and central mechanisms. There is, however, overwhelming evidence for a "nonclassical" RAS that results in the formation of novel peptide products with functional properties distinct from that of the ANG II-AT 1 receptor pathway (5,12,14,67,8...

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Section: Intracellular Formationsupporting

confidence: 77%

Review:Novel roles of nuclear angiotensin receptors and signaling mechanisms

Gwathmey

Alzayadneh

Pendergrass

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

108

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“…A study by Cao and colleagues indicated that high concentrations of albumin presented to PTC stimulated activation of renal RAAS. 170 Studies support that accumulation of non-esterified fatty acids (NEFA) and long chain acyl-co A transported into the tubule bound to albumin may accumulate in PTC and be a stimulus for PTC apoptosis. 161 In vitro studies using cell culture of both human and rodent PTC have shown that albumin can directly lead to cellular apoptosis via a caspase-9-mediated mitochondrial pathway and that megalin may be an important receptor for this pathway.…”

Section: Proteinuriamentioning

confidence: 99%

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Jepson

2016

Veterinary Clinics of North America: Small Animal Practice

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Abstract:In cats with chronic kidney disease (CKD), the most common histopathological finding is tubulointerstitial inflammation and fibrosis. However, these changes reflect a non-specific response of the kidney to any inciting injury. The risk of development of CKD in a patient is likely to reflect genetic predispositions, ageing, environmental and individual factors that influence decline in renal function over the course of a cat's life. However, there is still relatively little information about exactly which risk factors predispose a cat to develop CKD and these will be explored. Whilst many cats diagnosed with CKD have stable disease for many years, some cats show overtly progressive disease.

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“…Many studies indicate that, after kidney injury, intrarenal RAS is markedly activated because of concurrent upregulation of multiple RAS genes. 4,5 RAS activation contributes to kidney and cardiovascular injury through a range of mechanisms. In addition to regulating BP and hemodynamics, 6,7 angiotensin II, the principal and active mediator of RAS, activates TGF-b1 and NF-kB signaling and directly promotes renal inflammation and fibrosis.…”

mentioning

confidence: 99%

Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling

Zhou

Li²,

Hao³

et al. 2015

Journal of the American Society of Nephrology

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187

215

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Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor ( Extensive studies over the last several decades have established that activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. 1-3 RAS consists of several key components, including angiotensinogen (AGT), renin, angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1), and angiotensin II type 2 receptor (AT2). Many studies indicate that, after kidney injury, intrarenal RAS is markedly activated because of concurrent upregulation of multiple RAS genes. 4,5 RAS activation contributes to kidney and cardiovascular injury through a range of mechanisms. In addition to regulating BP and hemodynamics, 6,7 angiotensin II, the principal and active mediator of RAS, activates TGF-b1 and NF-kB signaling and directly promotes renal inflammation and fibrosis. 8-10 Studies using both genetic and pharmacologic approaches have confirmed the relevance and importance of RAS activation in the development and progression of CKD and cardiovascular disease. However, current anti-RAS therapy using ACE inhibitors (ACEIs) or angiotensin II receptor

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Albumin overload activates intrarenal renin–angiotensin system through protein kinase C and NADPH oxidase-dependent pathway

Abstract: Exposure of renal tubular epithelial cells with high levels of albumin triggers activation of RAS via a PKC-NADPH oxidase-dependent pathway.

Cited by 53 publications

References 38 publications

Review:Novel roles of nuclear angiotensin receptors and signaling mechanisms

Review:Novel roles of nuclear angiotensin receptors and signaling mechanisms

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

Multiple Genes of the Renin-Angiotensin System Are Novel Targets of Wnt/β-Catenin Signaling

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