Apamin inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration through suppressions of activated Akt and Erk signaling pathway.
The increased proliferation and migration of vascular smooth muscle cells (VSMC) are key process in the development of atherosclerosis lesions. Platelet-derived growth factor (PDGF) initiates a multitude of biological effects that contribute to VSMC proliferation and migration. Apamin, a component of bee venom, has been known to block the Ca(2+)-activated K(+) channels. However, the effects of apamin in the regulation PDGF-BB-induced VSMC proliferation and migration has not been identified. In this study, we investigate the inhibitory effect of apamin on PDGF-BB-induced VSMC proliferation and migration. Apamin suppressed the PDGF-BB-induced VSMC proliferation and migration with no apparent cytotoxic effect. In accordance with these findings, apamin induced the arrest of cell cycle progression at G0/G1 phase. Apamin also decreased the expressions of G0/G1 specific regulatory proteins including proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinases (CDK) 4, cyclin E and CDK2, as well as increased the expression of p21(Cip1) in PDGF-BB-induced VSMC. Moreover, apamin inhibited PDGF-BB-induced phosphorylation of Akt and Erk1/2. These results suggest that apamin plays an important role in prevention of vascular proliferation and migration through the G0/G1 cell cycle arrest by PDGF signaling pathway. Thus, apamin may be a promising candidate for the therapy of atherosclerosis.
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Jung-Yeon
JY
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Kyung-Hyun
KH
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Woo-Ram
WR
Lee
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Hyun-Jin
HJ
An
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Sun-Jae
SJ
Lee
Department of Agricultural Biology, National Academy of Agricultural Science, Suwon, Republic of Korea.
Sang-Mi
SM
Han
Department of Agricultural Biology, National Academy of Agricultural Science, Suwon, Republic of Korea.
Kwang-Gill
KG
Lee
Department of Physiology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Yoon-Yub
YY
Park
Cardiovascular Division, Department of Internal Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea.
Kee-Sik
KS
Kim
Cardiovascular Division, Department of Internal Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea. Electronic address: mdleeys@cu.ac.kr.
Young-Soo
YS
Lee
Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 705-718, Republic of Korea. Electronic address: kkpark@cu.ac.kr.
Kwan-Kyu
KK
Park
D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D000077214:Becaplermin; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D018797:Cell Cycle Proteins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D001030:Apamin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
Apamin; Cell cycle; Migration; Proliferation; VSMC