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.

Effects of Astragaloside IV on Action Potentials and Ionic Currents in Guinea-Pig Ventricular Myocytes

“…AS-IV, as one of its active elements, has been revealed its pharmacological mechanisms to some degree. Recent researches have suggested that AS-IV might protect from cardiomyopathy via diverse effects upon a variety of intracellular signaling pathways, including the activation of Src/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, 22) inhibiting tumor growth factor (TGF)-β1 23) and ERK1/2 signaling pathways, 24) upregulating superoxide dismutase-1 levels, 3,25) antioxidative and nitric oxide-inducing pathway, 26) and improving intracellular calcium handling. 27,28) The aim of our study is to clarify the basic electrophysiological effects of AS-IV on cardiac myocytes, and we have found that AS-IV prolonged APd, and decreased I K and I CaL in guinea-pig cardiac myocytes.…”

HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution

“…293 cell line: of kidney or adrenal gland origin and epithelial or neuronal phenotype? 293 cells have been considered the kidney embryonic epithelial cells (e.g., Ashokkumar et al, 2006;Cusick et al, 2010) or even fibroblasts (e.g., Cooper et al, 1998;Yung et al, 2012) and shown to express markers of a kidney developmental stage between the condensed mesenchyme and epithelial S-shaped body but not markers of the differentiated tubular segments, proximal tubules or collecting ducts (Torban and Goodyer, 1998). Moreover, an ectopic expression of transcription factor paired box gene 2 (PAX2), relevant to an early stage of nephrogenesis, modified vimentin, E-cadherin and Wilms tumor 1 expression in 293 cells in such a manner as it occurs during the mesenchymeepithelium transition of early nephrogenesis in vivo (Torban and Goodyer, 1998).…”

Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

“…This aglycone of astragaloside IV effectively enhances the antiviral response in human CD8+ T-lymphocytes through its distinct telomerase-promoting activity [28]. Furthermore, we demonstrated that CAG stimulates the phosphorylation of extracellular signal-regulated proteins in multiple cell lines and is absorbed via the intestinal epithelium [29,30]. Importantly, we have evaluated the pharmacological effects of CAG in neuronal cells as well as its effects on depression-like behaviors in mice.…”