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Oxidized LDL induces transcription factor activator protein-1 in rat mesangial cells.
Cell Biochem Funct. 2003 Sep; 21(3):249-56.CB

Abstract

It has been shown that oxidized low-density lipoprotein (ox-LDL), through the activation of glomerular cells, stimulates pathobiological processes involved in monocyte infiltration into the mesangium. The underlying molecular mechanisms are not fully understood. The present study showed that ox-LDL strongly induced AP-1 binding activity in rat mesangial cells (RMCs) in a dose- and time-dependent manner, reaching the maximal activation at 250 microg ml(-1) within 24 h. The results from mobility shift assays and Western blotting analysis revealed that this AP-1 binding increase involved c-Jun, but not c-Fos. Moreover, this ox-LDL-increased AP-1 binding was inhibited by several protein kinase (PK) inhibitors: the protein kinase C (PKC) inhibitor Bisindolylmaleimide I, the cAMP-dependent PK (PKA) inhibitor H89, and the tyrosine PK (PTK) inhibitor genistein. Protein phosphorylation represents mitogen-activated protein kinase (MAPK) activity. Therefore, we examined the role of ox-LDL on the activation of mesangial cell JNK/SAPK, the only recognized protein kinase that catalyses phosphorylation of c-Jun. The incubation of mesangial cells with ox-LDL induced phosphorylation of JNK1/SAPK dose dependently, with the maximal response at 150 microg ml(-1). This study demonstrates that multiple kinase activities are involved in the mechanism of ox-LDL-induced AP-1 activation in mesangial cells, and ox-LDL stimulates AP-1 through JNK-c-Jun other than MEK-c-Fos signalling pathway.

Authors+Show Affiliations

Division of Nephrology, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai 200032, People's Republic of China. Professor-wu@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12910478

Citation

Wu, Zhao-Long, et al. "Oxidized LDL Induces Transcription Factor Activator Protein-1 in Rat Mesangial Cells." Cell Biochemistry and Function, vol. 21, no. 3, 2003, pp. 249-56.
Wu ZL, Wang YC, Zhou Q, et al. Oxidized LDL induces transcription factor activator protein-1 in rat mesangial cells. Cell Biochem Funct. 2003;21(3):249-56.
Wu, Z. L., Wang, Y. C., Zhou, Q., Ge, Y. Q., & Lan, Y. (2003). Oxidized LDL induces transcription factor activator protein-1 in rat mesangial cells. Cell Biochemistry and Function, 21(3), 249-56.
Wu ZL, et al. Oxidized LDL Induces Transcription Factor Activator Protein-1 in Rat Mesangial Cells. Cell Biochem Funct. 2003;21(3):249-56. PubMed PMID: 12910478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidized LDL induces transcription factor activator protein-1 in rat mesangial cells. AU - Wu,Zhao-Long, AU - Wang,Yuan-Cheng, AU - Zhou,Qin, AU - Ge,Yu-Qiang, AU - Lan,Yang, PY - 2003/8/12/pubmed PY - 2004/5/7/medline PY - 2003/8/12/entrez SP - 249 EP - 56 JF - Cell biochemistry and function JO - Cell Biochem Funct VL - 21 IS - 3 N2 - It has been shown that oxidized low-density lipoprotein (ox-LDL), through the activation of glomerular cells, stimulates pathobiological processes involved in monocyte infiltration into the mesangium. The underlying molecular mechanisms are not fully understood. The present study showed that ox-LDL strongly induced AP-1 binding activity in rat mesangial cells (RMCs) in a dose- and time-dependent manner, reaching the maximal activation at 250 microg ml(-1) within 24 h. The results from mobility shift assays and Western blotting analysis revealed that this AP-1 binding increase involved c-Jun, but not c-Fos. Moreover, this ox-LDL-increased AP-1 binding was inhibited by several protein kinase (PK) inhibitors: the protein kinase C (PKC) inhibitor Bisindolylmaleimide I, the cAMP-dependent PK (PKA) inhibitor H89, and the tyrosine PK (PTK) inhibitor genistein. Protein phosphorylation represents mitogen-activated protein kinase (MAPK) activity. Therefore, we examined the role of ox-LDL on the activation of mesangial cell JNK/SAPK, the only recognized protein kinase that catalyses phosphorylation of c-Jun. The incubation of mesangial cells with ox-LDL induced phosphorylation of JNK1/SAPK dose dependently, with the maximal response at 150 microg ml(-1). This study demonstrates that multiple kinase activities are involved in the mechanism of ox-LDL-induced AP-1 activation in mesangial cells, and ox-LDL stimulates AP-1 through JNK-c-Jun other than MEK-c-Fos signalling pathway. SN - 0263-6484 UR - https://www.unboundmedicine.com/medline/citation/12910478/Oxidized_LDL_induces_transcription_factor_activator_protein_1_in_rat_mesangial_cells_ L2 - https://doi.org/10.1002/cbf.1015 DB - PRIME DP - Unbound Medicine ER -