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Small peptide PEP7 can decease Angiotensin II (Ang II) induced function through MAPK signaling pathway
Author(s) -
Liu Jun,
Zhang Dan,
Ji Hong,
Bajaj Bilkish,
Zheng Wei,
Samson Willis,
Sandberg Kathryn
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.936.1
Subject(s) - angiotensin ii , open reading frame , mapk/erk pathway , phosphorylation , microbiology and biotechnology , kinase , stimulation , hek 293 cells , receptor , renin–angiotensin system , extracellular , transfection , western blot , chemistry , biology , endocrinology , peptide sequence , biochemistry , gene , blood pressure
Sequence analysis of the 5′ leader sequence (5'LS) of the rat angiotensin type 1a receptor (rAT1aR) mRNA revealed a short open reading frame (sORF) within exon 2 (E2) which is in frame with the downstream major open reading frame that encodes the AT1aR. We found that the 7 amino acid peptide (PEP7) encoded by this sORF decreased 125I‐[Sar1, Ile8]Ang II specific binding by 23% in transfected human embryonic kidney‐293 (HEK‐293) cells expressing the rAT1aR under conditions in which the scrambled PEP7 (sPEP7) did not [dpm/μg protein: Vehicle, 162.2 ± 8.2, PEP7, 125.7 ± 7.0, sPEP7, 179.9 ± 3.9; n=3]. Furthermore, PEP7 inhibited angiotensin II (Ang II)‐induced activation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2) – defined as the phosphorylation of ERK1/2 (pERK1/2) with respect to total ERK1/2 (pERK/ERK) expression (measured by Western blot) in a dose‐ and time‐dependent manner. Ang II (100 nM) rapidly caused phosphorylation of ERK1/2, which was maximum after a 5 min exposure. Incubation of these cells with 2.5 μM PEP7 3 hours prior to Ang II stimulation for 5 min inhibited pERK1/2 generation by 62% [pERK1/2/ERK1/2 (AU): Ang II, 1.000 ± 0.0, Ang II+PEP7, 0.3812 ± 0.086, Ang II+sPEP7, 1.069 ± 0.18; n=2–3]. The inhibitory effect of PEP7 was not instantaneous since incubation of PEP7 20 min prior to stimulation with Ang II was without effect. Our findings suggest that PEP7 plays a regulatory role in controlling the expression and activity of the rAT1aR. [Supported by R01‐HL59502 (KS) and R01–066023 (WKS)]