Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.

Prolonged elevations of plasma aldosterone levels are associated with renal pathogenesis. We hypothesized that renal distress could be imposed by an augmented aldosterone-induced protein turnover challenging cellular protein degradation systems of the renal tubular cells. Cellular accumulation of sp...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Muhammad Umar Cheema, Helle Hasager Damkier, Jakob Nielsen, Ebbe Toftgaard Poulsen, Jan J Enghild, Robert A Fenton, Jeppe Praetorius
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f17beb439ba4539ad8bbba623f49866
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7f17beb439ba4539ad8bbba623f49866
record_format	dspace
spelling	oai:doaj.org-article:7f17beb439ba4539ad8bbba623f498662021-11-25T06:09:31ZDistal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.1932-620310.1371/journal.pone.0101258https://doaj.org/article/7f17beb439ba4539ad8bbba623f498662014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25000288/?tool=EBIhttps://doaj.org/toc/1932-6203Prolonged elevations of plasma aldosterone levels are associated with renal pathogenesis. We hypothesized that renal distress could be imposed by an augmented aldosterone-induced protein turnover challenging cellular protein degradation systems of the renal tubular cells. Cellular accumulation of specific protein aggregates in rat kidneys was assessed after 7 days of aldosterone administration. Aldosterone induced intracellular accumulation of 60 s ribosomal protein L22 in protein aggregates, specifically in the distal convoluted tubules. The mineralocorticoid receptor inhibitor spironolactone abolished aldosterone-induced accumulation of these aggregates. The aldosterone-induced protein aggregates also contained proteasome 20 s subunits. The partial de-ubiquitinase ataxin-3 was not localized to the distal renal tubule protein aggregates, and the aggregates only modestly colocalized with aggresome transfer proteins dynactin p62 and histone deacetylase 6. Intracellular protein aggregation in distal renal tubules did not lead to development of classical juxta-nuclear aggresomes or to autophagosome formation. Finally, aldosterone treatment induced foci in renal cortex of epithelial vimentin expression and a loss of E-cadherin expression, as signs of cellular stress. The cellular changes occurred within high, but physiological aldosterone concentrations. We conclude that aldosterone induces protein accumulation in distal renal tubules; these aggregates are not cleared by autophagy that may lead to early renal tubular damage.Muhammad Umar CheemaHelle Hasager DamkierJakob NielsenEbbe Toftgaard PoulsenJan J EnghildRobert A FentonJeppe PraetoriusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101258 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muhammad Umar Cheema Helle Hasager Damkier Jakob Nielsen Ebbe Toftgaard Poulsen Jan J Enghild Robert A Fenton Jeppe Praetorius Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
description	Prolonged elevations of plasma aldosterone levels are associated with renal pathogenesis. We hypothesized that renal distress could be imposed by an augmented aldosterone-induced protein turnover challenging cellular protein degradation systems of the renal tubular cells. Cellular accumulation of specific protein aggregates in rat kidneys was assessed after 7 days of aldosterone administration. Aldosterone induced intracellular accumulation of 60 s ribosomal protein L22 in protein aggregates, specifically in the distal convoluted tubules. The mineralocorticoid receptor inhibitor spironolactone abolished aldosterone-induced accumulation of these aggregates. The aldosterone-induced protein aggregates also contained proteasome 20 s subunits. The partial de-ubiquitinase ataxin-3 was not localized to the distal renal tubule protein aggregates, and the aggregates only modestly colocalized with aggresome transfer proteins dynactin p62 and histone deacetylase 6. Intracellular protein aggregation in distal renal tubules did not lead to development of classical juxta-nuclear aggresomes or to autophagosome formation. Finally, aldosterone treatment induced foci in renal cortex of epithelial vimentin expression and a loss of E-cadherin expression, as signs of cellular stress. The cellular changes occurred within high, but physiological aldosterone concentrations. We conclude that aldosterone induces protein accumulation in distal renal tubules; these aggregates are not cleared by autophagy that may lead to early renal tubular damage.
format	article
author	Muhammad Umar Cheema Helle Hasager Damkier Jakob Nielsen Ebbe Toftgaard Poulsen Jan J Enghild Robert A Fenton Jeppe Praetorius
author_facet	Muhammad Umar Cheema Helle Hasager Damkier Jakob Nielsen Ebbe Toftgaard Poulsen Jan J Enghild Robert A Fenton Jeppe Praetorius
author_sort	Muhammad Umar Cheema
title	Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
title_short	Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
title_full	Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
title_fullStr	Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
title_full_unstemmed	Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
title_sort	distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7f17beb439ba4539ad8bbba623f49866
work_keys_str_mv	AT muhammadumarcheema distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration AT hellehasagerdamkier distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration AT jakobnielsen distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration AT ebbetoftgaardpoulsen distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration AT janjenghild distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration AT robertafenton distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration AT jeppepraetorius distalrenaltubulesaredeficientinaggresomeformationandautophagyuponaldosteroneadministration
_version_	1718414111457411072

Distal renal tubules are deficient in aggresome formation and autophagy upon aldosterone administration.

Ejemplares similares