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Induction of heme oxygenase-1 is involved in anti-proliferative effects of paclitaxel on rat vascular smooth muscle cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2004 Aug 13; Vol. 321 (1), pp. 132-7. - Publication Year :
- 2004
-
Abstract
- In this study, we evaluated the possibility that the anti-proliferative effects of paclitaxel on vascular smooth muscle cells (VSMCs) of the rat might be due to the induction of HO-1 gene expression. Treatment of the cells with paclitaxel resulted in marked time- and dose-dependent inductions of HO-1 mRNA, followed by corresponding increases in HO-1 protein expression and HO enzymatic activities. Furthermore, paclitaxel rapidly activated the JNK, ERK, and p38 mitogen-activated protein kinase pathways. A specific inhibitor of JNK, SP600125, abolished paclitaxel-induced HO-1 mRNA expression, whereas PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38, had no significant effect. Finally, the suppression of platelet-derived growth factor induced VSMC proliferation was abolished by the HO inhibitor, ZnPP, as well as by the CO scavenger, hemoglobin. These results demonstrated that paclitaxel induces the expression of HO-1 via the JNK pathway in VSMC and that HO-1 expression might be responsible for the anti-proliferative effect of paclitaxel on VSMC.
- Subjects :
- Animals
Cells, Cultured
Gene Expression Regulation, Enzymologic drug effects
Heme Oxygenase (Decyclizing) metabolism
Heme Oxygenase-1
Mitogen-Activated Protein Kinases metabolism
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular drug effects
Phosphorylation
RNA, Messenger genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic drug effects
Cell Division drug effects
Heme Oxygenase (Decyclizing) genetics
Muscle, Smooth, Vascular enzymology
Paclitaxel pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 321
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 15358225
- Full Text :
- https://doi.org/10.1016/j.bbrc.2004.06.120