title: Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone.
abstract: The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2' ,7' -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway.
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala 690525, India.
authors.forename: Athira
authors.initials: A
authors.lastname: Omanakuttan
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala 690525, India.
authors.forename: Chinchu
authors.initials: C
authors.lastname: Bose
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala 690525, India.
authors.forename: Nanjan
authors.initials: N
authors.lastname: Pandurangan
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala 690525, India.
authors.forename: Geetha B
authors.initials: GB
authors.lastname: Kumar
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala 690525, India.
authors.forename: Asoke
authors.initials: A
authors.lastname: Banerji
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana P.O, Kollam, Kerala 690525, India. Electronic address: bipin@amrita.edu.
authors.forename: Bipin G
authors.initials: BG
authors.lastname: Nair
mesh_terms: D041721:3T3-L1 Cells; D035722:Aizoaceae / Q000737:chemistry; D000818:Animals; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004441:Ecdysterone / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D009569:Nitric Oxide; D004441:Ecdysterone; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Ecdysterone; Epidermal Growth Factor Receptor; Extracellular-signal-Regulated Kinase; Nitric Oxide; Nitric Oxide Synthase