Long Q et al, 2016: Autophagy activation protects shock wave induced renal tubular epithelial cell apoptosis may through modulation of Akt/ GSK-3β pathway.

Monday, 13 March 2017

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Long Q, Li X, He H, He D.
Department of Urology, First affiliated hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Abstract

PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is well documented to exert destructive effect to renal cells and its mechanism is not clear. Autophagy is one of cell basic response for stressful conditions and it is important to determine cell's fate. The aim of this study is to elucidate the role of autophagy in the process of shock wave-induced renal cells injury.
METHODS: NRK-52E cell, a rat renal tubular epithelial cell, was exposed to shock wave at the voltage of 14KV. GFP-LC3 puncta was used to monitor Autophagy flux in the process of shock wave injury. Autophagic relative proteins, such as light chain 3 (LC3), beclin-1 and p62, were also examined. Cell variability and apoptosis were detected when inhibition autophagy with 3-methyladenine (3MA) or stimulating its activity with rapamycin during the process of shock wave injury. The role of Akt/ GSK-3β and its connection with autophagy in the process of shock wave injury were also investigated. RESULTS: Shock wave was confirmed to activate autophagy in renal cells, which was manifested in LC3-II turnover, beclin-1 induction and degradation of p62. Inhibition autophagy enhanced cell damage or apoptosis, whereas its stimulating was able to exert protection from shock wave injury. Akt/ GSK-3β, a cell-survival signaling pathway, can also be activated during the process. And its activation could be suppressed by blockade autophagy.
CONCLUSION: Autophagy is a self-protective response for renal cells from shock wave injury. The cyto-protection of autophagy may be connected with modulation Akt/ GSK-3β pathway.

Int J Biol Sci. 2016 Nov 24;12(12):1461-1471. FULL ARTICLE

Comments 1

Peter Alken on Monday, 13 March 2017 11:05

This paper - like 21 of the 29 references - concentrates more on apoptosis and phagocytosis than on ESWL. In previous studies the authors had used 100 shock waves at a voltage of 18 kV for similar studies (Li X, He D, Zhang L, et al. Pyrrolidine dithiocarbamate attenuate shock wave induced MDCK cells injury via inhibiting nuclear factor-kappa B activation. Urol Res. 2007; 35:193-199); in the present study the power was reduced to 14 kv probably because of the massive cell death rate under the experimental conditions: After application of 200 shocks only 50 % of cells survived shown in MTT assays and quantitative nuclear staining analysis. With 300 shocks only 30% survived. It is not clear if the shocks were applied with varying frequency “with impulse rates of 50, 100, 150,200,250 and 300 shock waves per minute” as stated in the material and method section or if simply the number of shocks were increased. The results show that Rapamycin, an mTOR inhibitor which is used clinically to prevent organ transplant rejection could alleviate the ESWL effects to a small extent. But the setting does not allow a conclusion if this could be of clinical relevance.

This paper - like 21 of the 29 references - concentrates more on apoptosis and phagocytosis than on ESWL. In previous studies the authors had used 100 shock waves at a voltage of 18 kV for similar studies (Li X, He D, Zhang L, et al. Pyrrolidine dithiocarbamate attenuate shock wave induced MDCK cells injury via inhibiting nuclear factor-kappa B activation. Urol Res. 2007; 35:193-199); in the present study the power was reduced to 14 kv probably because of the  massive cell death rate under the experimental conditions:  After application of 200 shocks only 50 % of cells survived shown in MTT assays and quantitative nuclear staining analysis. With 300 shocks only 30% survived.  It is not clear if the shocks were applied with varying frequency “with impulse rates of 50, 100, 150,200,250 and 300 shock waves per minute” as stated in the material and method section or if simply the number of shocks were increased. The results show that Rapamycin, an mTOR inhibitor which is used clinically to prevent organ transplant rejection could alleviate the ESWL effects to a small extent. But the setting does not allow a conclusion if this could be of clinical relevance.

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