Abstract
Angiotensin II exerts a cardinal role in the pathogenesis of hypertension and renal injury via action of angiotensin II type 1 (AT1) receptors. Local renin-angiotensin system (RAS) activity is essential for the mechanisms mediating pathophysiological functions. Proximal tubular angiotensinogen and tubular AT1 receptors are augmented by intrarenal angiotensin II. Caveolin 1 plays an important role as a regulatory molecule for the compartmentalization of redox signaling events through angiotensin II–induced NADPH oxidase activation in the kidney. A role for the renin-angiotensin system in the development and/or maintenance of hypertension has been demonstrated in spontaneously hypertensive rats (SHRs). Many effects of angiotensin II are dependent on the AT1 stimulation of reactive oxygen species (ROS) production by NADPH oxidase. Angiotensin II upregulation stimulates oxidative stress in proximal tubules from SHR. The NADPH oxidase 4 (Nox4) is abundantly expressed in kidney proximal tubule cells. Induction of the stress response includes synthesis of heat shock protein 70, a molecular chaperone that has a critical role in the recovery of cells from stress and in cytoprotection, guarding cells from subsequent insults. HSP70 chaperones function in part by driving the molecular triage decision, which determines whether proteins enter the productive folding pathway or result in client substrate ubiquitination and proteasomal degradation. This review examines regulation of losartan-mediated antioxidative stress responses by the chaperone HSP70 in proximal tubule cells of spontaneously hypertensive rats.
Similar content being viewed by others
References
Anwar A, Siegel D, Kepa JK, Ross D (2002) Interaction of the molecular chaperone Hsp70 with human NAD(P)H: quinone oxidoreductase. J Biol Chem 277:14060–14067
Assimon VA, Gillies AT, Rauch JN, Gestwicki JE (2013) Hsp70 protein complexes as drug targets. Curr Pharm Des 19:404–417
Aufricht C, Lu E, Thulin G, Kashgarian M, Siegel NJ, Van Why SK (1998) ATP releases HSP-72 from protein aggregates after renal ischemia. Am J Physiol Renal Physiol 274:F268–F274
Babelova A, Avaniadi D, Jung O, Fork C, Beckmanen J, Kosowski J, Weissmann N, Anilkumar N, Shah AM, Schaefer L, Schröder K, Brandes RP et al (2012) Role of Nox4 in murine models of kidney disease. Free Radic Biol Med 53:842–853
Beck FX, Neuhofer W, Müller E (2000) Molecular chaperones in the kidney: distribution, putative roles, and regulation. Am J Physiol Renal Physiol 279(2):F203–F215
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313
Block K, Eid A, Griendling KK, Lee DY, Wittrant Y, Gorin Y (2008) Nox4 NAD (P)H oxidase mediates Src-dependent tyrosine phosphorylation of PDK-1 in response to angiotensin II: role in mesangial cell hypertrophy and fibronectin expression. J Biol Chem 283:24061–24076
Bocanegra V, Manucha PMR, Cacciamani V, Vallés PG (2010) Caveolin 1 and Hsp70 interaction in microdissected proximal tubules from spontaneously hypertensive rats as effect of losartan. J Hypertens 28(1):143–155
Borges TJ, Wieten L, Van Herwijnen MJ, Broere F, Van Der Zee R, Bonorino C, Van Eden W (2012) The anti-inflammatory mechanisms of Hsp70. Front Immunol 3:95
Braam B, Mitchell KD, Fox J, Navar LG (1993) Proximal tubular secretion of angiotensin II in rats. Am J Phys 264(5 Pt 2):F891–F898
Brown DI, Griendling KK (2009) Nox proteins in signal transduction. Free Radic Biol Med 47:1239–1253
Casarini DE, Boim MA, Stella RC, Krieger-Azzolini MH, Krieger JE, Schor N (1997) Angiotensin I-converting enzyme activity in tubular fluid along the rat nephron. Am J Phys 272(3 Pt 2):F405–F409
Chappell MC (2012) Nonclassical renin-angiotensin system and renal function. Compr Physiol. 2(4):2733–2752
Chebotareva N, Bobkova I, Shilov E (2017) Heat shock proteins and kidney disease: perspectives of HSP therapy. Cell Stress and Chaperones 22:319–343
Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD (2001) Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 269:131–140
Cohen AW, Hnasko R, Schubert W, Lisanti MP (2004) Role of caveolae and caveolins in health and disease. Physiol Re 84:1341–1379
Cohen DM, Wasserman JC, Gullans SR (1991) Immediate early gene and HSP70 expression in hyperosmotic stress in MDCK cells. Am J Physiol Cell Physiol 261:C594–C601
Costantino VV, Bocanegra V, Cacciamani V, Lorenzo AFG, Benardon ME, Vallés PG (2019) Losartan through Hsp70 avoids angiotensin II induced mesenchymal epithelial transition in proximal tubule cells from spontaneously hypertensive rats. Cell Physiol Biochem 53(4):713–730
Crowley SD, Gurley SB, Oliverio MI, Pazmino AK, Griffiths R, Flannery PJ, Spurney RF, Kim HS, Smithies O, Le TH, Coffman TM (2005) Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin–angiotensin system. J Clin Invest 115:1092–1099
Cucoranu I, Clempus R, Dikalova A, Phelan PJ, Ariyan D, Dikalov S, Sorescu D (2005) NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. Circ Res 97:900–907
Cuevas S, Zhang Y, Yang Y, Escano C, Asico L, Jones JE, Armando I, Jose PA (2012) Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygen species production. Hypertension 59:446–452
Demand J, Alberti S, Patterson C, Hohfeld J (2001) Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr Biol 11:1569–1577
Drab M, Verkade P, Elger M, Kasper M, Lohn M, Lauterbach B, Menne J, Lindschau C, Mende F, Luft FC, Schedl A, Haller H, Kurzchalia TV (2001) Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin 1 gene-disrupted mice. Science 303:2449–2452
Emami A, Schwartz JH, Borkan SC (1991) Transient ischemia or heat stress induces a cytoprotectant protein in rat kidney. Am J Physiol Renal Fluid Electrolyte Physiol. 260:F479–F485
Garvin JL (1991) Angiotensin stimulates bicarbonate transport and Na+/K+-ATPase in rat proximal straight tubules. J Am Soc Nephrol 1:1146–1152
Geiszt M, Kopp JB, Petal V (2000) Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci U S A 97:8010–8014
Geiszt M (2006) NADPH oxidases: new kids on the block. Cardiovasc Res 71:289–299
Gellai R, Hodrea J, Lenart L, Hosszu A, Koszegi S, Balogh D, Ver A, Banki NF, Fulop N, Molnar A, Wagner L, Vannay A, Szabo AJ, Fekete A (2016) Role of O-linked N-acetylglucosamine modification in diabetic nephropathy. Am J Physiol Renal Physiol. 311:F1172–F1181
Gil Lorenzo AF, Bocanegra V, Benardon ME, Cacciamani V, Vallés PG (2014) Hsp70 regulation on Nox4/p22phox and cytoskeletal integrity as an effect of losartan in vascular smooth muscle cells. Cell Stress Chaperones 19(1):115–134
Gil Lorenzo AF, Costantino VV, Appiolaza ML, Cacciamani V, Benardon ME, Bocanegra V, Vallés PG (2015) Heat shock protein 70 and CHIP promote Nox4 ubiquitination and degradation within the losartan antioxidative effect in proximal tubule cells. Cell Physiol Biochem 36(6):2183–2197
Gill PS, Wilcox CS (2006) NADPH oxidases in the kidney. Antioxid Redox Signal 8:1597–1607
Hackenthal E, Paul M, Ganten D, Taugner R (1990) Morphology, physiology, and molecular biology of renin secretion. Physiol Rev 70:1067–1116
Hannken T, Schroeder R, Stahl RAK, Wolf G (1998) Angiotensin II-mediated expression of p27kip 1 and induction of cellular hypertrophy in renal tubular cells depend on the generation of oxygen radicals. Kidney Int 54:1923–1193
Harris PJ, Navar LG (1985) Tubular transport responses to angiotensin II. Am J Physiol Renal Physiol. 248:F621–F630
Hitomi H, Kiyomoto H, Nishiyama A (2007) Angiotensin II and oxidative stress. Curr Opin Cardiol 22:311–31545
Ichihara A, Kobori H, Nishiyama A, Navar LG (2004) Renal renin-angiotensin system. Contrib Nephrol 143:117–130. Review
Ishizaka N, Griendling KK, Lassegue B, Alexander RW (1998) Angiotensin II type 1 receptor: relationship with caveolae and caveolin after initial agonist stimulation. Hypertension. 32:459–46626
Javkhedkar AA, Lokhandwala MF, Banday AA (2012) Defective nitric oxide production impairs angiotensin II-induced Na+-K+-ATPase regulation in spontaneously hypertensive rats. Am J Physiol Renal Physiol 302:F47–F51
Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE (2009) Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14(1):105–111
Kaushal GP (2012) Autophagy protects proximal tubular cells from injury and apoptosis. Kidney Int 82:1250–1253
Kim MG, Jung Cho E, Won Lee J, Sook Ko Y, Young Lee H, Jo SK, Cho WY, Kim HK (2014) The heat-shock protein-70-induced renoprotective effect is partially mediated by CD4+CD25+Foxp3+ regulatory T cells in ischemia/reperfusion-induced acute kidney injury. Kidney Int 85:62–71
Kobori H, Ozawa Y, Satou R, Katsurada A, Miyata K, Ohashi N, Hase N, Suzaki Y, Sigmund CD, Navar LG (2007) Kidney-specific enhancement of ANG II stimulates endogenous intrarenal angiotensinogen in gene-targeted mice. Am J Physiol Renal Physiol. 293:F938–F945
Komatsuda A, Wakui H, Imai H, Nakamoto Y, Miura AB, Itoh H, Tashima Y (1992) Renal localization of the constitutive 73-kDa heat-shock protein in normal and PAN rats. Kidney Int 41:1204–1212
Komlosi P, Fuson AL, Fintha A, Peti-Peterdi J, Rosivall L, Warnock DG, Bell PD (2003) Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport. Hypertension. 42:195–199
Lapointe MS, Sodhi CH, BatlleD (2002) Na+/H+ exchange activity and NHE-3 expression in renal tubules from the spontaneously hypertensive rat. Hypertension. 62;157–165
Lassegue B, Griendling KK (2010) NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol 30:653–661
Leclerc PC, Auger-Messier M, Lanctot PM, Escher E, Leduc R, Guillemette G (2002) A polyaromatic caveolin-binding-like motif in the cytoplasmic tail of the type 1 receptor for angiotensin II plays an important role in receptor trafficking and signaling. Endocrinology. 143(12):4702–4710
Li H, Han W, Villar VA, Keever LB, Lu Q, Hopfer U, Quinn MT, Felder RA, Jose PA, Yu P (2009) D1-like receptors regulate NADPH oxidase activity and subunit expression in lipid raft microdomains of renal proximal tubule cells. Hypertension. 53:1054–1061
Li XC, Carretero OA, Navar LG, Zhuo JL (2006) AT1 receptor-mediated accumulation of extracellular angiotensin II in proximal tubule cells: role of cytoskeleton microtubules and tyrosine phosphatases. Am J Physiol Renal Physiol. 291:F375–F383
Li XC, Navar LG, Shao Y, Zhuo JL (2007) Genetic deletion of AT1a receptors attenuates intracellular accumulation of angiotensin II in the kidney of AT1a receptor-deficient mice. Am J Physiol Renal Physiol. 293:F586–F593
Li XC, Victor G, Miguel-Qin E, Zhuo JL (2014) Role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II in the proximal tubule of the kidney. Am J Physiol Renal Physiol 307(8):F949–F961
Li XC, Zhuo JL (2008) In vivo regulation of AT1a receptor-mediated intracellular uptake of [125I]Val5-angiotensin II in the kidneys and adrenal glands of AT1a receptor-deficient mice. Am J Physiol Renal Physiol. 294:F293–F302
Li XC, Zhuo JL (2014) Mechanisms of AT1 receptor-mediated uptake of angiotensin II by proximal tubule cells: a novel role of the multiligand endocytic receptor megalin. Am J Physiol Renal Physiol. 307(2):F222–F233
Liu F, Wei CC, Wu SJ, Chenier I, Zhang SL, Filep JG, Ingelfinger JR, Chan JSD (2009) Apocynin attenuates tubular apoptosis and tubulointerstitial fibrosis in transgenic mice independent of hypertension. Kidney Int 75:156–166
Lyle AN, Deshpande NN, Taniyama Y, Seidel-Rogol B, Pounkova L, Du P, Papaharalambus C, Lassègue B, Griendling KK (2009) Poldip2, a novel regulator of Nox4 and cytoskeletal integrity in vascular smooth muscle cells. Circ Res 105:249–259
Majid DS, Nishiyama A, Jackson KE, Castillo A (2005) Superoxide scavenging attenuates renal responses to ANG II during nitric oxide synthase inhibition in anesthetized dogs. Am J Physiol Renal Physiol. 288:F412–F419
Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62:670–684
Mayer MP (2013) Hsp70 chaperone dynamics and molecular mechanism. Trends Biochem Sci 38:507–514
Mayer MP (2018) Intra-molecular pathways of allosteric control in Hsp70s. Phil. Trans. R. Soc. Lond B Biol Sci. Review
McDonough H, Patterson C (2003) CHIP: a link between the chaperone and proteasome systems. Cell Stress Chaperones 8:303–308
Mendelsohn FA (1982) Angiotensin II: evidence for its role as an intrarenal hormone. Kidney Int Suppl 12:S78–S81
Molitoris BA (1991) Ischemia-induced loss of epithelial polarity: potential role of the actin cytoskeleton. Am J Physiol Renal Fluid Electrolyte Physiol. 260:F769–F778
Mori T, Cowley AW Jr (2003) Angiotensin II-NAD(P)H oxidase-stimulated superoxide modifies tubulovascular nitric oxide cross-talk in renal outer medulla. Hypertension. 42:588–593
Müller E, Neülhofer W, Ohno A, Rucker S, Thürau K, Beck F-X (1996) Heat shock proteins HSP25, HSP60, HSP72, HSP73 in isoosmotic cortex and hyperosmotic medulla of rat kidney. Pflügers Arch. 431:608–617
Müller E, Neülhofer W, Burger-Kentischer A, Ohno A, Thürau K, Beck F-X (1998) Effects of long-term changes in medullary osmolality on heat shock proteins HSP25, HSP60, HSP72 and HSP73 in the rat kidney. Pflügers Arch 435:705–712
Navar LG, Imig JD, Zou L, Wang C-T (1997) I ntrarenal production of angiotensin II. Sem Nephrol 17:412–422
Navar LG, Nishiyama A (2001) Intrarenal formation of angiotensin II. Contrib Nephrol:1–15
Navar L, Harrison-Bernard LM, Nishiyama A, Kobori H (2002) Regulation of intrarenal angiotensin II in hypertension. Hypertension 39(2 Pt 2):316–322
Navar LG (2004) The intrarenal renin-angiotensin system in hypertension. Kidney Int 65(4):1522–1532
Navar LG. (2005) The role of the kidneys in hypertension. J Clin Hypertens (Greenwich.) 7(9):542–9. Review
Neühofer W, Lugmayr K, Fraek M-L, Beck F-X (2001) Regulated over-expression of heat shock protein 72 protects Madin-Darby canine kidney cells from the detrimental effects of high urea concentration. J Am Soc Nephrol 12:2565–2571
New DD, Block K, Bhandhari B, Gorin Y, Abboud HE (2012) IGF-I increases the expression of fibronectin by Nox4-dependent Akt phosphorylation in renal tubular epithelial cells. Am J Physiol Cell Physiol 302:C122–C130
Nishiyama A, Seth DM, Navar LG (2003) Angiotensin II type 1 receptor-mediated augmentation of renal interstitial fluid angiotensin II in angiotensin II-induced hypertension. JHypertens. 21(10):1897–1903
Nistala R, Whaley-Connell A, Sowers JR (2008) Redox control of renal function and hypertension. Antioxid Redox Signal 10:2047–2089
O’Neill S, Harrison EM, Ross JA, Wigmore SJ, Hughes J (2014) Acute kidney injury. Exp Nephrol 126:167–174
Pace PE, Peskin AV, Konigstorfer A, Jasoni CJ, Winterbourn CC, Hampton MB (2018) Peroxiredoxin interaction with the cytoskeletal-regulatory protein CRMP2: investigation of a putative redox relay. Free Radic Biol Med 129:383–393
Pedrosa R, Villar VAM, Pascua AM, Simao S, Hopfer U, Jose PA, Soares- da-Silva P (2008) H2O2 stimulation of the Cl-/HCO3-exchanger by angiotensin II and angiotensin II type 1 receptor distribution in membrane microdomains. Hypertension. 51:1332–1338
Pockley AG (2003) Heat shock proteins as regulators of the immune response. Lancet. 362:469–476
Quinn MT, Evans T, Loetterle LR, Jesaitis AJ, Bokoch GM (1993) Translocation of Rac correlates with NADPH oxidase activation. Evidence for equimolar translocation of oxidase components. J Biol Chem. 268:20983–20987
Rhyu DY, Yang Y, Ha H, Lee GT, Song JS, Uh ST, Lee HB (2005) Role of reactive oxygen species in TGF-beta1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol 16:667–675
Rodrigues-Díez R, Carvajal-González G, Sánchez-López E, Rodríguez-Vita J, Rodrigues Díez R, Selgas R, Ortiz A, Egido J, Mezzano S, Ruiz-Ortega M (2008) Pharmacological modulation of epithelial mesenchymal transition caused by angiotensin II. Role of ROCK and MAPK pathways. Pharm Res 25:2447–2461
Ruete MC, Carrizo LC, Valles PG (2008) Na+/K+-ATPase stabilization by Hsp70 in the outer stripe of the outer medulla in rats during recovery from a low-protein diet. Cell Stress Chaperones 13(2):157–167
Schlecht R, Erbse AH, Bukau B, Mayer MP (2011) Mechanics of Hsp70 chaperones enables differential interaction with client proteins. Nat Struct Mol Biol 18:345–351
Schnermann JB, Traynor T, Yang T, Huang YG, Oliverio MI, Coffman T, Briggs JP (1997) Absence of tubuloglomerular feedback responses in AT1A receptor-deficient mice. Am J Phys 273:F315–F320
Schober A, Müller E, Thurau K, Beck F-X (1997) The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones. Pflügers Arch 434:292–299
Seikaly MG, Arant BS Jr, Seney FD Jr (1990) Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest 86(4):1352–1357
Selemidis S, Sobey CG, Wingler K, Schmidt HH, Drummond GR (2008) NADPH oxidases in the vasculature: molecular features, roles in disease and pharmacological inhibition. Pharmacol Ther 120:254–291
Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, Hattori M, Sakaki Y, Sumimoto H (2001) A novel superoxide-producing NAD(P)H oxidase in kidney. J Biol Chem 276:1417–1423
Silva E, Soares-da-Silva (2007) Reactive oxygen species and the regulation of renal Na+-K+-ATPase in opossum kidney cells. Am J Physiol Regul Integr Comp Physiol 293:R1764–R1770
Silva GB, Garvin JL (2008) Angiotensin II-dependent hypertension increases Na transport-related oxygen consumption by the thick ascending limb. Hypertension. 52:1091–1098
Silva GB, Garvin JL (2010) Rac1 mediates NaCl-induced superoxide generation in the thick ascending limb. Am J Physiol Renal Physiol. 298:F421–F425
Sobotta MC, Liou W, Stocker S et al (2015) Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat Chem Biol 11:64–70
Sone M, Albrecht GJ, Dörge A, Thürau K, Beck F-X (1993) Osmotic adaptation of renal medullary cells during transition from chronic diuresis to antidiuresis. Am J Physiol Renal Fluid Electrolyte Physiol 264:F722–F729
Sotgia F, Razani B, Bonuccelli G, Schubert W, Battista M, Lee H, Capozza F, Schubert AL, Minetti C, Buckley JT, Lisanti MP (2002) Intracellular retention of glycosylphosphatidyl inositol-linked proteins in caveolin-deficient cells. Mol Cell Biol 22:3905–3926
Takac I, Schroder K, Zhang L et al (2011) The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem 286:13304–13313
Ushio-Fukai M, Alexander RW (2006) Caveolin-dependent angiotensin II type1 receptor signaling in vascular smooth muscle. Hypertension 48:797–803
Van Why SK, Hildebrandt F, Ardito T, Mann AS, Siegel NJ, Kashgarian M (1992) Induction and intracellular localization of HSP-72 after renal ischemia. Am J Physiol Renal Fluid Electrolyte Physiol. 263:F769–F775
Wang Z, Gall JM, Bonegio RG, Havasi A, Hunt CR, Sherman MY, Schwartz JH, Borkan SC (2011) Induction of heat-shock protein 70 inhibits ischemic renal injury. Kidney Int 79:861–870
Welch WJ (1993) How cells respond to stress. Sci Am 268:56–64
White BH, Sidhu A (1998) Increased oxidative stress in renal proximal tubules of the spontaneously hypertensive rat: a mechanism for defective dopamine D1A receptor/G-protein coupling. J Hypertension 16:1659–1665
Wickner S, Maurizi MR, Gottesman S (1999) Posttranslational quality control: folding, refolding, and degrading proteins. Science. 286:1888–1893
Wyse BD, Prior IA, Qian H, Morrow IC, Nixon S, Muncke C, Kurzchalia TV, Thomas WG, Parton RG, Hancock JF (2003) Caveolin interacts with the angiotensin II type 1 receptor during exocytic transport but not at the plasma membrane. J Biol Chem 278(26):23738–23746
Yamabhai M, Anderson RG (2002) Second cysteine-rich region of epidermal growth factor receptor contains targeting information for caveolae/rafts. J Biol Chem 277(28):24843–24846
Yang Y, Fiskus W, Yong B, Atadja P, Takahashi Y, Pandita TK et al (2013) Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy. Proc Natl Acad Sci USA 110:6841–6846
Yoneda M, Sanada H, Yatabe J, Midorikawa S, Hashimoto S, Sasaki M, Katoh T, Watanabe T, Andrews PM (2005) Differential effects of angiotensin II type-1 receptor antisense oligonucleotides on renal function in spontaneously hypertensive rats. Hypertension. 46:58–65
Zhao YY, Liu Y, Stan RV, Fan L, Gu Y, Dalton N, Chu PH, Peterson K, Ross J Jr, Chien KR (2002) Defects in caveolin 1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci U S A 99:11375–11380
Zuiderweg ER, Hightower LE, Gestwicki JE (2017) The remarkable multivalency of the Hsp70 chaperones. Cell Stress Chaperones 22:173–189
Zhuo JL, Imig JD, Hammond TG, Orengo S, Benes E, Navar LG (2002) Ang II accumulation in rat renal endosomes during Ang II-induced hypertension: role of AT1 receptor. Hypertension. 39(1):116–121
Zhuo JL, Carretero OA, Li XC (2006) Effects of AT1a receptor-mediated endocytosis of extracellular angiotensin II on activation of nuclear factor-KB in proximal tubule cells. Ann N Y Acad Sci 1091:336–345
Zhuo JL, Li XC (2011) New insights and perspectives on intrarenal renin-angiotensin system: focus on intracrine/intracellular angiotensin II. Peptides. 32(7):1551–1565
Zhuo JL, Li XC (2013) Proximal nephron. Compr Physiol 3(3):1079–1123
Zou LX, Hymel A, Imig JD, Navar LG (1996) Renal accumulation of circulating angiotensin II in angiotensin II-infused rats. Hypertension 27(3Pt2):658–662
Zuo L, Ushio-Fukai M, Ikeda S, Hilenski L, Patrushev N, Alexander RW (2004) Microtubules regulate angiotensin II type 1 receptor and Rac1 localization in caveolae/lipid rafts. Role in redox signaling. Arterioscler Thromb Vasc Biol 24(7):1223–1228
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Vallés, P.G., Bocanegra, V., Costantino, V.V. et al. The renal antioxidative effect of losartan involves heat shock protein 70 in proximal tubule cells. Cell Stress and Chaperones 25, 753–766 (2020). https://doi.org/10.1007/s12192-020-01119-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12192-020-01119-8