View : 683 Download: 0
The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect
- Title
- The protective effect of klotho against contrast-associated acute kidney injury via the antioxidative effect
- Authors
- Oh, Hyung Jung; Oh, Hyewon; Nam, Bo Young; You, Je Sung; Ryu, Dong-Ryeol; Kang, Shin-Wook; Chung, Yong Eun
- Ewha Authors
- 류동열; 오형중
- SCOPUS Author ID
- 류동열; 오형중
- Issue Date
- 2019
- Journal Title
- AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
- ISSN
- 1931-857X
1522-1466
- Citation
- AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY vol. 317, no. 4, pp. F881 - F889
- Keywords
- acute kidney injury; apoptosis; oxidative stress
- Publisher
- AMER PHYSIOLOGICAL SOC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- As oxidative stress is one major factor behind contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of klotho against CA-AKI via the antioxidative effect. In in vitro experiments, cells (NRK-52E) were divided into the following three groups: control, iopamidol, or iopamidol + recombinant klotho (rKL) groups. Moreover, cell viability was measured with the Cell Counting Kit-8 assay, and oxidative stress was examined with 2',7'-dichlorodihydrofluorescein diacetate fluorescence intensity. RTPCR and Western blot analysis were performed to assess propidium iodide klotho expression, and Bax-to-Bcl-2 and apoptosis ratios were evaluated with annexin V/Hoechst 33342 staining. Furthermore, we knocked down the klotho gene using siRNA to verify the endogenous effect of klotho. In our in vivo experiments, oxidative stress was evaluated with the thiobarbituric acid-reactive substance assay, and apoptosis was evaluated with the Bax-to-Bcl-2 ratio and cleaved caspase-3 immunohistochemistry. Additionally, cell and tissue morphology were investigated with transmission electron microscopy. In both in vitro and in vivo experiments, mRNA and protein expression of klotho significantly decreased in CA-AKI mice compared with control mice, whereas oxidative stress and apoptosis markers were significantly increased in CA-AKI mice. However, rKL supplementation mitigated the elevated apoptotic markers and oxidative stress in the CA-AKI mouse model and improved cell viability. In contrast, oxidative stress and apoptotic markers were more aggravated when the klotho gene was knocked down. Moreover, we found more cytoplasmic vacuoles in the CA-AKI mouse model using transmission electron microscopy but fewer cytoplasmic vacuoles in rKL-supplemented cells. The present study shows that klotho in proximal tubular cells can protect against CA-AKI via an antioxidative effect.
- DOI
- 10.1152/ajprenal.00297.2018
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML