PMID- 17971303 OWN - NLM STAT- MEDLINE DCOM- 20071218 LR - 20091119 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 364 IP - 4 DP - 2007 Dec 28 TI - Important role of apoptosis signal-regulating kinase 1 in ischemic acute kidney injury. PG - 1043-9 AB - We investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Blood urea nitrogen (BUN) and serum creatinine were significantly higher in ASK1+/+ mice than in ASK1-/- mice after I/R injury. Renal histology of ASK1+/+ mice showed significantly greater tubular necrosis and degradation. In ASK1-/- mice, phosphorylation of ASK1, JNK, and p38K, and the number of TUNEL-positive cells and infiltrated leukocytes decreased after I/R injury. Apoptotic changes were significantly decreased in cultured renal tubular epithelial cells (TECs) from ASK1-/- mice under hypoxic condition. Transfection with dominant-active ASK1 induced apoptosis in TECs. Protein expression of monocyte chemoattractant protein-1 (MCP-1) was significantly weaker in ASK1-/- mice after I/R injury. Transfection with dominant negative-ASK1 significantly decreased MCP-1 production in TECs. These results demonstrated that ASK1 is activated in I/R-induced AKI, and blockage of ASK1 attenuates renal tubular apoptosis, MCP-1 expression, and renal function. FAU - Terada, Yoshio AU - Terada Y AD - Department of Nephrology and Blood Purification, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo 113-8519, Japan. yterada.kid@tmd.ac.jp FAU - Inoshita, Seiji AU - Inoshita S FAU - Kuwana, Hitoshi AU - Kuwana H FAU - Kobayashi, Takahiko AU - Kobayashi T FAU - Okado, Tomokazu AU - Okado T FAU - Ichijo, Hidenori AU - Ichijo H FAU - Sasaki, Sei AU - Sasaki S LA - eng PT - Journal Article DEP - 20071029 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Apoptosis Regulatory Proteins) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5) SB - IM MH - Animals MH - *Apoptosis MH - Apoptosis Regulatory Proteins/metabolism MH - Kidney/*blood supply/*metabolism/pathology MH - Kidney Tubules/*metabolism/pathology MH - MAP Kinase Kinase Kinase 5/*metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Reperfusion Injury/metabolism/*pathology EDAT- 2007/11/01 09:00 MHDA- 2007/12/19 09:00 CRDT- 2007/11/01 09:00 PHST- 2007/10/21 00:00 [received] PHST- 2007/10/22 00:00 [accepted] PHST- 2007/11/01 09:00 [pubmed] PHST- 2007/12/19 09:00 [medline] PHST- 2007/11/01 09:00 [entrez] AID - S0006-291X(07)02305-4 [pii] AID - 10.1016/j.bbrc.2007.10.122 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2007 Dec 28;364(4):1043-9. doi: 10.1016/j.bbrc.2007.10.122. Epub 2007 Oct 29.