Endoplasmic reticulum stress in proteinuric kidney disease

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Endoplasmic reticulum stress in proteinuric kidney disease Andrey V. Cybulsky Kidney International Volume 77, Issue 3, Pages 187-193 (February 2010) DOI: 10.1038/ki.2009.389 Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 1 Protein folding, quality control, and signaling in the endoplasmic reticulum (ER). Solid arrow indicates enzymatic catalysis, dotted arrow indicates an interaction, dashed arrow indicates transport. ATF4, activating transcription factor-4; ATF6, activating transcription factor-6; eIF2α, eukaryotic translation initiation factor-2α subunit; EDEM, endoplasmic reticulum degradation-enhancing α-mannosidase-like protein; ERAD, endoplasmic reticulum-associated degradation; GRP94, glucose-regulated protein 94; IRE1, inositol requiring-1α; JNK, c-Jun N-terminal kinase; PERK, PKR-like ER kinase; UGGT, UDP-glucose:glycoprotein glucosyltransferase; UPR, unfolded protein response; XBP1, X-box-binding protein-1. Adapted from Chevet et al.1 Kidney International 2010 77, 187-193DOI: (10.1038/ki.2009.389) Copyright © 2010 International Society of Nephrology Terms and Conditions

Figure 2 Endoplasmic reticulum (ER) stress in experimental membranous nephropathy (passive Heymann nephritis; PHN). (a) ER stress is increased in C5b-9-mediated podocyte injury. Glomeruli were isolated from normal rats (control) and from rats with PHN on day 14, and lysates were immunoblotted with antibodies to BiP, GRP94, or phospho-eIF2α. (b) Preconditioning of rats with a subnephritogenic dose of adriamycin (Adr) or tunicamycin (Tun) reduces proteinuria in PHN. Rats were untreated (Untr), or were injected with adriamycin or tunicamycin to upregulate ER stress proteins. Four days later, rats were injected with nephritogenic antibody to induce PHN (day 0). Urine protein excretion was measured on days 0, 7, 9, and 13. (c) Scheme illustrating the effect of ER stress preconditioning on glomerular injury (proteinuria). UPR, unfolded protein response. Panels a and b are from Cybulsky et al.,16,17 with permission. Kidney International 2010 77, 187-193DOI: (10.1038/ki.2009.389) Copyright © 2010 International Society of Nephrology Terms and Conditions