Effects of dehydroepiandrosterone on mitogen-activated protein kinase in human aortic smooth muscle cells

Autor: Nozomu Tamai, Yasunari Jin-No, Akihiko Yoneyama, Takayuki Yoshimata, Yoshinobu Kamiya
Rok vydání: 1999
Předmět:
Male
MAPK/ERK pathway
medicine.medical_specialty
Platelet-derived growth factor
Basic fibroblast growth factor
8-Bromo Cyclic Adenosine Monophosphate
Dehydroepiandrosterone
Dinoprostone
Muscle
Smooth
Vascular
General Biochemistry
Genetics and Molecular Biology
chemistry.chemical_compound
Epidermal growth factor
Internal medicine
Cyclic AMP
medicine
Humans
General Pharmacology
Toxicology and Pharmaceutics
Growth Substances
Protein kinase A
Aorta
Cells
Cultured
biology
Colforsin
Intracellular Signaling Peptides and Proteins
General Medicine
Enzyme Activation
Endocrinology
chemistry
Mitogen-activated protein kinase
Calcium-Calmodulin-Dependent Protein Kinases
cardiovascular system
biology.protein
Carrier Proteins
human activities
hormones
hormone substitutes
and hormone antagonists
Platelet-derived growth factor receptor
Zdroj: Life Sciences. 65:431-440
ISSN: 0024-3205
DOI: 10.1016/s0024-3205(99)00264-7
Popis: The objective of the present study was to determine whether dehydroepiandrosterone (DHEA) modifies growth factor-induced mitogen-activated protein kinase (MAPK) activation, based on our previous study demonstrating that DHEA attenuates fetal calf serum-induced proliferation in human male aortic smooth muscle cells (human male aortic SMCs). Human male aortic SMCs were used for this study. Platelet-derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), but not insulin-like growth factor-1 (IGF-1), stimulated MAPK activity. Only MAPK activation induced by PDGF-BB was reduced by pretreatment with DHEA, although DHEA did not affect the MAPK activation induced by EGF or bFGF. The basal and PDGF-stimulated MAPK activity were decreased by two types of cyclic AMP (cAMP) elevating agents and increased by cAMP-dependent protein kinase (PKA) inhibitor in human male aortic SMCs, suggesting that cAMP regulates MAPK negatively. The intracellular cAMP was increased by PDGF-BB. The increase of cAMP by PDGF-BB was augmented by pretreatment with DHEA, although DHEA alone did not affect cAMP. Neither EGF nor bFGF affected cAMP with and without DHEA pretreatment. Secretion of PGE2 induced by PDGF was augmented by pretreatment with DHEA. Stimulatory effects of DHEA on the production of PGE2 and cAMP were partially canceled by aromatase inhibitor and completely canceled by indomethacin or selective inhibitor of cyclooxygenase-2. These results suggest that DHEA inhibited MAPK activation induced by PDGF-BB via PGE2 overproduction and subsequent cAMP-dependent pathway in human male aortic SMCs.
Databáze: OpenAIRE
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