title: Application of the ERK signaling pathway inhibitor PD98059 in long-term in vivo experiments.
abstract: The aim of this study was to explore methods by which the ERK signaling pathway inhibitor PD98059 (PD) could be used in long-term in vivo experiments. Forty healthy New Zealand rabbits were randomly divided into blank control, model control, PD low-dose, PD high-dose, PD blank, dimethyl sulfoxide (DMSO) control, DMSO blank, and positive control groups. The corresponding treatments were administered to each experimental group over the course of four weeks, after which, total ERK1/2 and ERK5 protein levels, protein phosphorylation, and gene expression were measured in myocardial tissues. Treatment of rabbits with Adriamycin (doxorubicin) resulted in the significant overall differences in ERK1/2 and ERK5 phosphorylation (P < 0.05). Compared with the model control group, changes in phosphorylated ERK1/2 and phosphorylated ERK5 were lowest in the PD high-dose group (P < 0.05). No significant differences in total protein and mRNA levels of myocardial ERK1/2 and ERK5 were detected between the groups after four weeks (P > 0.05). Continuous intravenous injection of PD98059 significantly reduced phosphorylation of ERK1/2 and that of ERK5. In conclusion, Adriamycin-induced myocardiopathy and abnormal ERK signaling might constitute a valuable model foruse in long-term experiments. These methods may provide a theoretical basis for related in vivo studies of long duration.
authors.affiliation: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Cai
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Tang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one