[HTML][HTML] MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis
SK Jo, WY Cho, SA Sung, HK Kim, NH Won - Kidney international, 2005 - Elsevier
SK Jo, WY Cho, SA Sung, HK Kim, NH Won
Kidney international, 2005•ElsevierMEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation
and apoptosis. 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 …
and apoptosis. 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 …
MEK inhibitor, U0126, attenuates cisplatin-induced renal injury by decreasing inflammation and apoptosis.
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-α (TNF-α (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-α 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-α–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.
Elsevier