RRC ID 44485
Author Ishizuka T, Goshima H, Ozawa A, Watanabe Y.
Title Stimulation of α₁-adrenoceptor or angiotensin type 1 receptor enhances DNA synthesis in human-induced pluripotent stem cells via Gq-coupled receptor-dependent signaling pathways.
Journal Eur. J. Pharmacol.
Abstract Stimulation of either α₁-adrenoceptor or angiotensin type 1 receptor (AT₁ receptor) induces proliferation of mouse induced pluripotent stem (iPS) cells. Both α₁-adrenoceptor and AT₁ receptor are guanine nucleotide-binding protein q polypeptide (Gq)-coupled receptors. However, it is not fully understood whether stimulation of these Gq-coupled receptors exert a similar effect in human iPS cells, i.e. proliferation of human iPS cells. In this study, we evaluated the involvement of α₁-adrenoceptor and AT₁ receptor in the DNA synthesis of human iPS cells. Treatment with either l-phenylephrine (a selective α₁-adrenoceptor agonist) or angiotensin II (Ang II) significantly increased DNA synthesis in human iPS cells. Enhanced DNA synthesis was significantly inhibited by pretreatment with protein kinase C (PKC) inhibitors, mitogen-activated protein kinase kinase (MEK) inhibitor, or phosphatidylinositol-3 phosphate kinase (PI3K) inhibitor. Treatment with either l-phenylephrine or Ang II significantly increased Akt and p44/42 MAPK phosphorylation. Short interfering RNA (siRNA) directed against Gq significantly inhibited DNA synthesis and phosphorylation of Akt and p44/42 MAPK enhanced by l-phenylephrine or Ang II. These results suggest that stimulation of α₁-adrenoceptor or AT₁ receptor may enhance DNA synthesis in human iPS cells via Gq-coupled receptor-dependent signaling pathways.
Volume 714(1-3)
Pages 202-9
Published 2013-8-15
DOI 10.1016/j.ejphar.2013.06.003
PII S0014-2999(13)00469-X
PMID 23792040
MeSH Adrenergic alpha-1 Receptor Agonists / pharmacology Adrenergic alpha-1 Receptor Antagonists / pharmacology Angiotensin II / pharmacology Angiotensin II Type 1 Receptor Blockers / pharmacology Animals Cell Line DNA / biosynthesis* GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism* Gene Expression Regulation / drug effects Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / drug effects Induced Pluripotent Stem Cells / metabolism* Mice Phosphorylation / drug effects Receptor, Angiotensin, Type 1 / metabolism* Receptors, Adrenergic, alpha-1 / metabolism* Signal Transduction / drug effects*
IF 3.04
Times Cited 4
Human and Animal Cells