title: Astragaloside IV and cycloastragenol stimulate the phosphorylation of extracellular signal-regulated protein kinase in multiple cell types.
abstract: Two Chinese herb-derived small molecule telomerase activators, astragaloside IV (AG-IV) and cycloastragenol (CAG), have recently been shown to improve the proliferative response of CD8+ T lymphocytes from HIV-infected patients by upregulating telomerase activity. Here, we examined the signaling mechanism of AG-IV and CAG. Telomerase activity in human embryonic kidney HEK293 fibroblasts was increased upon treatment with increasing concentrations of AG-IV or CAG. Both compounds induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) in a time- and dose-dependent manner in HEK293 cells and HEK-neo keratinocytes. AG-IV and CAG also stimulated ERK phosphorylation in other cell lines of lung, brain, mammary, endothelial, and hematopoietic origins. Use of selective inhibitors and dominant negative mutants revealed the involvement of c-Src, MEK (ERK kinase), and epidermal growth factor receptor in CAG-induced ERK phosphorylation. Our data indicate that AG-IV and CAG may exert their cellular effects through the activation of the Src/MEK/ERK pathway.
authors.affiliation: Biotechnology Research Institute and Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Yung
authors.forename: Wing See
authors.initials: WS
authors.lastname: Lam
authors.forename: Maurice K C
authors.initials: MK
authors.lastname: Ho
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Hu
authors.forename: Fanny C F
authors.initials: FC
authors.lastname: Ip
authors.forename: Haihong
authors.initials: H
authors.lastname: Pang
authors.forename: Allison C
authors.initials: AC
authors.lastname: Chin
authors.forename: Calvin B
authors.initials: CB
authors.lastname: Harley
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.forename: Yung H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D027883:Astragalus Plant / Q000737:chemistry*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001940:Breast / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012502:Sapogenins / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D012502:Sapogenins; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D066246:ErbB Receptors; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019098:Telomerase; C061014:cycloastragenol