Angiotensin-(1-7) enhances angiotensin II induced phosphorylation of ERK1/2 in mouse bone marrow-derived dendritic cells.
It is well known that angiotensin-(1-7) (Ang-(1-7)) counterbalances vasoconstrictive and proliferative functions of angiotensin II (Ang II), some of those actions are via inhibition of Ang II induced activation of mitogen-activated protein kinases(MAPK). This study investigated the effects of Ang-(1-7) on Ang II-mediated cell signaling pathways in mouse bone marrow-derived dendritic cells (DC). The expression of receptor Mas and angiotensin-converting enzyme-related carboxypeptidase (ACE2) mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR); activation of MAPK was detected by immunoblotting after incubation of dendritic cells with Ang II in the presence or absence of Ang-(1-7), valsartan, PD123319, and D-Ala(7)-Ang-(1-7). Ang II rapidly (5 min, 10(-7) mol/L) stimulated phosphorylation of extracellular signal-related kinase (ERK1/2); this effect was partially inhibited by Ang II type 1 (AT1) receptor antagonist valsartan and significantly attenuated by Ang II type 2 (AT2) receptor antagonist PD123319. Ang-(1-7) alone also induced phosphorylation of ERK1/2; co-treatment of Ang-(1-7) and Ang II markedly enhanced ERK1/2 phosphorylation, the enhancement was eliminated by the Ang-(1-7) receptor antagonist D-Ala(7)-Ang-(1-7). Both Ang-(1-7) and Ang II had no effect on p38 and c-Jun N-terminal kinase (JNK) phosphorylation. In conclusion, Ang II stimulates ERK1/2 phosphorylation via AT2 receptor in mouse DC, Ang-(1-7) enhances this effect. Generation of Ang-(1-7) by DC could thereby counteract on the pro-inflammatory function of locally generated Ang II.
Nie
Wencheng
W
Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310003, PR China.
Yan
Hui
H
Li
Shan
S
Zhang
Yun
Y
Yu
Fulin
F
Zhu
Weiguo
W
Fan
Fangyan
F
Zhu
Jianhua
J
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D010446:Peptide Fragments; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D000803:Angiotensin I; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)