Naked Polyamidoamine Polymers Intrinsically Inhibit Angiotensin II-Mediated EGFR and ErbB2 Transactivation in a Dendrimer Generation- and Surface Chemistry-Dependent Manner.
作者： Saghir Akhtar , Ahmed Z El-Hashim , Bindu Chandrasekhar , Sreeja Attur , Ibrahim F. Benter
DOI: 10.1021/ACS.MOLPHARMACEUT.6B00045
关键词:
摘要: The effects of naked polyamidoamine (PAMAM) dendrimers on renin–angiotensin system (RAS) signaling via Angiotensin (Ang) II-mediated transactivation the epidermal growth factor receptor (EGFR) and closely related family member ErbB2 (HER2) were investigated. In primary aortic vascular smooth muscle cells, a cationic fifth-generation (G5) PAMAM dendrimer dose- time-dependently inhibited Ang II/AT1 receptor-mediated EGFR as well their downstream extracellular-regulated kinase 1/2 (ERK1/2). Inhibition even occurred at noncytotoxic concentrations short (1 h) exposure times was dependent generation (G7 > G6 G5 G4) surface group chemistry (amino carboxyl hydroxyl). Mechanistically, inhibition nonreceptor tyrosine Src. This novel, early onset, intrinsic biological action inhibitors I...
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