Aldosterone and angiotensin II induce protein aggregation in renal proximal tubules

Physiological Reports

Muhammad U. Cheema¹  Ebbe T. Poulsen²  Jan J. Enghild²  Ewout Hoorn³  Robert A. Fenton¹ 

[1] Department of Biomedicine, Membranes & InterPrET, Health, Aarhus University, Aarhus, Denmark;Department of Molecular Biology and Genetics, iNano, Science and Technology, Aarhus University, Aarhus, Denmark;Department of Internal Medicine, Nephrology, Erasmus Medical Center, Rotterdam, the Netherlands

关键词: Aggresome;    autophagy;    protein aggregation;    proximal tubules;   

DOI  :  10.1002/phy2.64

来源: Wiley

【 摘 要 】

Abstract

Renal tubules are highly active transporting epithelia and are at risk of protein aggregation due to high protein turnover and/or oxidative stress. We hypothesized that the risk of aggregation was increased upon hormone stimulation and assessed the state of the intracellular protein degradation systems in the kidney from control rats and rats receiving aldosterone or angiotensin II treatment for 7 days. Control rats formed both aggresomes and autophagosomes specifically in the proximal tubules, indicating a need for these structures even under baseline conditions. Fluorescence sorted aggresomes contained various rat keratins known to be expressed in renal tubules as assessed by protein mass spectrometry. Aldosterone administration increased the abundance of the proximal tubular aggresomal protein keratin 5, the ribosomal protein RPL27, ataxin-3, and the chaperone heat shock protein 70-4 with no apparent change in the aggresome–autophagosome markers. Angiotensin II induced aggregation of RPL27 specifically in proximal tubules, again without apparent change in antiaggregating proteins or the aggresome–autophagosome markers. Albumin endocytosis was unaffected by the hormone administration. Taken together, we find that the renal proximal tubules display aggresome formation and autophagy. Despite an increase in aggregation-prone protein load in these tubules during hormone treatment, renal proximal tubules seem to have sufficient capacity for removing protein aggregates from the cells.

【 授权许可】

CC BY   
© 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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