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Endoplasmic Reticulum Stress as a Target of Therapy Against Oxidative Stress and Hypoxia

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Studies on Renal Disorders

Abstract

Oxidative stress or hypoxia is the major disturbance that leads to endoplasmic reticulum (ER) dysfunction. The ER maintains protein homeostasis, including the regulation of the concentration, conformation, folding, and trafficking of client proteins. ER dysfunction by the disturbances such as oxidative stress, referred to as ER stress, induces intracellular stress responses, called the unfolded protein response (UPR). The UPR initially serves as an adaptive response, but also induces apoptosis in cells under severe or prolonged ER stress. The linkage of ER stress with oxidative stress or hypoxia, both of which are pathogenic, indicates the potential pathophysiological significance of ER stress across a wide range of diseases. Accumulating evidence indicates that ER stress contributes to glomerular and tubular damages in patients with acute and chronic kidney diseases. In glomeruli, podocyte or mesangial dysfunction tends to induce the adaptive UPR, which involves ER chaperone expression and the attenuation of protein translation to maintain ER homeostasis and ensure cell survival. In tubules, apoptosis, resulting from epithelial cell damage, is caused by the pro-apoptotic UPR, at least in part. These findings emphasize not only the importance of ER stress as a new progression factor but also the interesting future possibility of renoprotective strategy targeting ER stress. These therapeutic approaches may act by breaking the vicious cycle of oxidative stress, hypoxia, and ER stress.

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Acknowledgments

This work was supported by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (19590939) and a grant from the Kidney Foundation, Japan (JKFB09-2).

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Authors and Affiliations

  1. Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1, Hongo Bunkyo-ku, Tokyo, 113-8655, Japan

    Reiko Inagi

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Correspondence to Reiko Inagi .

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Editors and Affiliations

  1. Graduate School of Medicine, Division of Molecular Medicine and Thera, Tohoku University, Seiryo-machi 2-1, Sendai, 980-8575, Japan

    Toshio Miyata

  2. Medizinische Klinik IV, Universitätsklinikum Erlangen, Krankenhausstr. 12, Erlangen, 91054, Germany

    Kai-Uwe Eckardt

  3. Graduate School of Medicine &, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Tokyo, 113-8655, Japan

    Masaomi Nangaku

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Inagi, R. (2011). Endoplasmic Reticulum Stress as a Target of Therapy Against Oxidative Stress and Hypoxia. In: Miyata, T., Eckardt, KU., Nangaku, M. (eds) Studies on Renal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60761-857-7_33

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