$Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury$
Código QR

Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury

Changhui Diao, Lei Wang, Hao Liu, Yang Du, Xiuheng Liu Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China Background: Ischemia-reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Numerous therapeutic approaches...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Diao C, Wang L, Liu H, Du Y, Liu X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Autophagy Ischemia-reperfusion Renal Aged Apoptosis Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/13b66257e2714118bf447738136a83f6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:13b66257e2714118bf447738136a83f6
record_format	dspace
spelling	oai:doaj.org-article:13b66257e2714118bf447738136a83f62021-12-02T07:37:02ZAged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury1178-1998https://doaj.org/article/13b66257e2714118bf447738136a83f62019-03-01T00:00:00Zhttps://www.dovepress.com/aged-kidneys-are-refractory-to-autophagy-activation-in-a-rat-model-of--peer-reviewed-article-CIAhttps://doaj.org/toc/1178-1998Changhui Diao, Lei Wang, Hao Liu, Yang Du, Xiuheng Liu Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China Background: Ischemia-reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Numerous therapeutic approaches for I/R injury have been studied, including autophagy, particularly in animal models of renal I/R injury derived from young or adult animals. However, the precise role of autophagy in renal ischemia-reperfusion in the aged animal model remains unclear. The purpose of this study was to demonstrate whether autophagy has similar effects on renal I/R injury in young and aged rats. Materials and methods: All rats were divided into two age groups (3 months and 24 months) with each group being further divided into four subgroups (sham, I/R, I/R+Rap (rapamycin, an activator of autophagy), I/R+3-MA (3-methyladenine, an inhibitor of autophagy)). The I/R+Rap and I/R+3-MA groups were intraperitoneally injected with rapamycin and 3-MA prior to ischemia. We then measured serum levels of urea nitrogen, creatinine and assessed damage in the renal tissue. Immunohistochemistry was used to assess LC3-II and caspase-3, and Western blotting was used to evaluate the autophagy-related proteins LC3-II, Beclin-1 and P62. Apoptosis and autophagosomes were evaluated by TUNEL and transmission electron microscopy, respectively. Results: Autophagy was activated in both young and aged rats by I/R and enhanced by rapamycin, although the level of autophagy was lower in the aged groups. In young rats, the activation of autophagy markedly improved renal function, reduced apoptosis in the renal tubular epithelial cells and the injury score in the renal tissue, thereby exerting protective effects on renal I/R injury. However, this level of protection was not present in aged rats. Conclusion: Our data indicated that the activation of autophagy was ineffective in aged rat kidneys. These discoveries may have major implications in that severe apoptosis in aged kidneys might be refractory to antiapoptotic effect induced by the activation of autophagy. Keywords: autophagy, ischemia-reperfusion, renal, aged, apoptosis, rapamycin, 3-methyladenineDiao CWang LLiu HDu YLiu XDove Medical PressarticleAutophagyIschemia-reperfusionRenalAgedApoptosisGeriatricsRC952-954.6ENClinical Interventions in Aging, Vol Volume 14, Pp 525-534 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Autophagy Ischemia-reperfusion Renal Aged Apoptosis Geriatrics RC952-954.6
spellingShingle	Autophagy Ischemia-reperfusion Renal Aged Apoptosis Geriatrics RC952-954.6 Diao C Wang L Liu H Du Y Liu X Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
description	Changhui Diao, Lei Wang, Hao Liu, Yang Du, Xiuheng Liu Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China Background: Ischemia-reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Numerous therapeutic approaches for I/R injury have been studied, including autophagy, particularly in animal models of renal I/R injury derived from young or adult animals. However, the precise role of autophagy in renal ischemia-reperfusion in the aged animal model remains unclear. The purpose of this study was to demonstrate whether autophagy has similar effects on renal I/R injury in young and aged rats. Materials and methods: All rats were divided into two age groups (3 months and 24 months) with each group being further divided into four subgroups (sham, I/R, I/R+Rap (rapamycin, an activator of autophagy), I/R+3-MA (3-methyladenine, an inhibitor of autophagy)). The I/R+Rap and I/R+3-MA groups were intraperitoneally injected with rapamycin and 3-MA prior to ischemia. We then measured serum levels of urea nitrogen, creatinine and assessed damage in the renal tissue. Immunohistochemistry was used to assess LC3-II and caspase-3, and Western blotting was used to evaluate the autophagy-related proteins LC3-II, Beclin-1 and P62. Apoptosis and autophagosomes were evaluated by TUNEL and transmission electron microscopy, respectively. Results: Autophagy was activated in both young and aged rats by I/R and enhanced by rapamycin, although the level of autophagy was lower in the aged groups. In young rats, the activation of autophagy markedly improved renal function, reduced apoptosis in the renal tubular epithelial cells and the injury score in the renal tissue, thereby exerting protective effects on renal I/R injury. However, this level of protection was not present in aged rats. Conclusion: Our data indicated that the activation of autophagy was ineffective in aged rat kidneys. These discoveries may have major implications in that severe apoptosis in aged kidneys might be refractory to antiapoptotic effect induced by the activation of autophagy. Keywords: autophagy, ischemia-reperfusion, renal, aged, apoptosis, rapamycin, 3-methyladenine
format	article
author	Diao C Wang L Liu H Du Y Liu X
author_facet	Diao C Wang L Liu H Du Y Liu X
author_sort	Diao C
title	Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
title_short	Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
title_full	Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
title_fullStr	Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
title_full_unstemmed	Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
title_sort	aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/13b66257e2714118bf447738136a83f6
work_keys_str_mv	AT diaoc agedkidneysarerefractorytoautophagyactivationinaratmodelofrenalischemiareperfusioninjury AT wangl agedkidneysarerefractorytoautophagyactivationinaratmodelofrenalischemiareperfusioninjury AT liuh agedkidneysarerefractorytoautophagyactivationinaratmodelofrenalischemiareperfusioninjury AT duy agedkidneysarerefractorytoautophagyactivationinaratmodelofrenalischemiareperfusioninjury AT liux agedkidneysarerefractorytoautophagyactivationinaratmodelofrenalischemiareperfusioninjury
_version_	1718399263843549184

Aged kidneys are refractory to autophagy activation in a rat model of renal ischemia-reperfusion injury

Ejemplares similares