title: Downregulation of the antioxidant protein peroxiredoxin 2 contributes to angiotensin II-mediated podocyte apoptosis.
abstract: Podocytes have a significant role in establishing selective permeability of the glomerular filtration barrier. Sustained renin-angiotensin-aldosterone system activation is crucial to the pathogenesis of podocyte injury, but the mechanisms by which angiotensin II modulates podocyte survival due to physiological or injurious stimuli remain unclear. Here, we used proteomic analysis to find new mediators of angiotensin II-induced podocyte injury. Antioxidant protein peroxiredoxin 2 expression was decreased in cultured podocytes stimulated with angiotensin II. Peroxiredoxin 2 was found to be expressed in podocytes in vivo, and its expression was decreased in the glomeruli of rats transgenic for angiotensin II type 1 receptors in a podocyte-specific manner, or in rats infused with angiotensin II. Downregulation of peroxiredoxin 2 in podocytes resulted in increased reactive oxygen species release, protein overoxidation, and inhibition of the Akt pathway. Both treatment with angiotensin II and downregulation of peroxiredoxin 2 expression led to apoptosis of podocytes. Thus, peroxiredoxin 2 is an important modulator of angiotensin II-induced podocyte injury.
authors.affiliation: Department of Medicine D, Division of General Internal Medicine and Nephrology, University Hospital Münster, Münster, Germany; Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsiang-Hao
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Medical Research Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Department of Medicine D, Division of General Internal Medicine and Nephrology, University Hospital Münster, Münster, Germany.
authors.forename: Giovana S
authors.initials: GS
authors.lastname: Di Marco
authors.affiliation: Department of Anatomy and Cell Biology, University of Greifswald, Greifswald, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Endlich
authors.affiliation: Institute for Medical Physics and Biophysics, University of Münster, Münster, Germany.
authors.forename: Jasna
authors.initials: J
authors.lastname: Peter-Katalinić
authors.affiliation: Department of Medicine D, Division of General Internal Medicine and Nephrology, University Hospital Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weide
authors.affiliation: Department of Medicine D, Division of General Internal Medicine and Nephrology, University Hospital Münster, Münster, Germany. Electronic address: Hermann.Pavenstaedt@ukmuenster.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D055104:Infusions, Subcutaneous; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism*; D010766:Phosphorylation; D050199:Podocytes / Q000201:enzymology* / Q000473:pathology; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: C544065:AGTR1 protein, human; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D054464:Peroxiredoxins; D051057:Proto-Oncogene Proteins c-akt