PMID- 16891764 OWN - NLM STAT- MEDLINE DCOM- 20061003 LR - 20190911 IS - 1347-8613 (Print) IS - 1347-8613 (Linking) VI - 101 IP - 4 DP - 2006 Aug TI - Protein kinase C beta inhibitor LY333531 attenuates intercellular adhesion molecule-1 and monocyte chemotactic protein-1 expression in the kidney in diabetic rats. PG - 335-43 AB - In vitro studies have shown that activation of protein kinase C (PKC) is a key mediator of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in a range of cell types and in response to high glucose, however, its role in the in vivo setting has not been clearly delineated. Streptozotocin-induced diabetic rats were treated with the PKC-beta isoform inhibitor LY333531 for 8 weeks. LY333531 treatment significantly attenuated increased urinary albumin excretion rate and glomerular volume and tubulointerstitial injury index as well as elevated PKC activity and PKC-beta protein expression in the kidney. Level of malondialdehyde was markedly higher and antioxidant enzyme activity such as superoxide diamutase and catalase as well as glutathione peroxidase were significantly lower in the kidney from diabetic rats than that of the control group. LY333531 administration could remit these changes. Increased macrophages recruitment as well as ICAM-1 and MCP-1 protein expression in the kidney were significantly inhibited by LY333531 in diabetic rats. It is concluded that mechanism of renoprotection of LY333531 may be correlated, at least partly, with suppression of increased macrophages recruitment and overexpression of ICAM-1 and MCP-1 in diabetic rats. FAU - Wu, Yonggui AU - Wu Y AD - Department of Nephropathy, the First Affiliated Hospital of AnHui Medical University, Hefei, China. wygxll@ah163.com FAU - Wu, Guozhong AU - Wu G FAU - Qi, Xiangming AU - Qi X FAU - Lin, Hui AU - Lin H FAU - Qian, Hao AU - Qian H FAU - Shen, Jijia AU - Shen J FAU - Lin, Shantan AU - Lin S LA - eng PT - Journal Article DEP - 20060805 PL - Japan TA - J Pharmacol Sci JT - Journal of pharmacological sciences JID - 101167001 RN - 0 (Blood Glucose) RN - 0 (Chemokine CCL2) RN - 0 (Indoles) RN - 0 (LY 338522) RN - 0 (Maleimides) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.- (Peroxidases) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (Protein Kinase C beta) SB - IM MH - Albuminuria/prevention & control MH - Animals MH - Blood Glucose/metabolism MH - Blotting, Western MH - Body Weight/drug effects MH - Chemokine CCL2/*biosynthesis MH - Diabetes Mellitus, Experimental/complications/drug therapy/*metabolism MH - Immunohistochemistry MH - Indoles/*pharmacology MH - Intercellular Adhesion Molecule-1/*biosynthesis MH - Kidney/*drug effects/metabolism/pathology MH - Kidney Glomerulus/drug effects/metabolism/pathology MH - Macrophages/drug effects/immunology/metabolism MH - Maleimides/*pharmacology MH - Malondialdehyde/antagonists & inhibitors/metabolism MH - Nephritis, Interstitial/complications/drug therapy MH - Organ Size/drug effects MH - Oxidative Stress/drug effects MH - Peroxidases/antagonists & inhibitors/metabolism MH - Protein Kinase C/antagonists & inhibitors/metabolism MH - Protein Kinase C beta MH - Rats MH - Rats, Wistar EDAT- 2006/08/08 09:00 MHDA- 2006/10/04 09:00 CRDT- 2006/08/08 09:00 PHST- 2006/08/08 09:00 [pubmed] PHST- 2006/10/04 09:00 [medline] PHST- 2006/08/08 09:00 [entrez] AID - JST.JSTAGE/jphs/FP0050896 [pii] AID - 10.1254/jphs.fp0050896 [doi] PST - ppublish SO - J Pharmacol Sci. 2006 Aug;101(4):335-43. doi: 10.1254/jphs.fp0050896. Epub 2006 Aug 5.