MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis
- Authors
- Jo, SK; Cho, WY; Sung, SA; Kim, HK; Won, NH
- Issue Date
- Feb-2005
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- cisplatin; ERK; TNF-alpha; inflammation; caspase; apoptosis
- Citation
- KIDNEY INTERNATIONAL, v.67, no.2, pp 458 - 466
- Pages
- 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- KIDNEY INTERNATIONAL
- Volume
- 67
- Number
- 2
- Start Page
- 458
- End Page
- 466
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/19845
- DOI
- 10.1111/j.1523-1755.2005.67102.x
- ISSN
- 0085-2538
1523-1755
- Abstract
- Background. Although inflammation and apoptosis are known to play important roles in cisplatin nephrotoxicity, the exact intracellular signaling mechanisms are not well understood. Recent reports that extracellular signal-regulated kinase (ERK1/2) pathway mediates cisplatin-induced caspase activation and apoptosis in cultured renal tubular cells led us to investigate the effect of MAPK/ERK kinase (MEK) inhibitor, an immediate upstream of ERK1/2 in cisplatin-induced acute renal failure (ARF) in mice. Methods. The effect of MEK/ERK1/2 inhibition on kidney tumor necrosis factor-alpha (TNF-alpha (gene expression, inflammation, the activation of tissue caspases, and apoptosis were examined in addition to its effects on renal function and histology in cisplatin-induced ARF in mice. Results. Pretreatment of MEK inhibitor, U0126, decreased ERK1/2 phosphorylation following cisplatin administration with significant functional and histologic protection. This beneficial effect was accompanied by decrease in TNF-alpha gene expression level and inflammation, as well as in caspase 3 activity and apoptosis. Conclusion. These data provide evidence that ERK1/2 pathway functions as an upstream signal for TNF-alpha-mediated inflammation and caspase 3-mediated apoptosis in cisplatin-induced ARF in mice and suggest that ERK1/2 can be a novel therapeutic target in cisplatin nephrotoxicity.
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- Appears in
Collections - 1. Basic Science > Department of Pathology > 1. Journal Articles
- 2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
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