Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging

Biochemical Pharmacology
Gaeun ParkKi Won Lee

Abstract

While skin aging is a naturally occurring process by senescence, exposure to ultraviolet (UV) radiation accelerates wrinkle formation and sagging of skin. UV induces skin aging by degrading collagen via activating matrix metalloproteinases (MMPs). In this study, we show that coumestrol, a metabolite of the soybean isoflavone daidzein, has a preventive effect on skin photoaging in three-dimensional human skin equivalent model. Coumestrol inhibited UVB-induced MMP-1 expression and activity. Whole human kinase profiling assay identified FLT3 kinase as a novel target protein of coumestrol in UVB-induced signaling pathway in skin. Coumestrol suppresses FLT3 kinase activity, and subsequently, Ras/MEK/ERK and Akt/p70 ribosomal S6 kinase pathway. This suppresses AP-1 activity and in turn, diminishes MMP-1 gene transcription. Using X-ray crystallography, the binding of coumestrol to FLT3 was defined and implied ATP-competitive inhibition. Residues Lys644 and Phe830 showed local changes to accommodate coumestrol in the ATP-binding pocket. 4-APIA, a pharmacological inhibitor of FLT3, inhibited MMP-1 expression and induced signal transduction changes similar to coumestrol. Taken together, coumestrol inhibits UVB-induced MMP-1 expression by...Continue Reading

References

Sep 1, 1989·Journal of the American Academy of Dermatology·J UittoD R Olsen
Oct 1, 1996·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·A J Whitmarsh, R J Davis
Nov 14, 1997·The New England Journal of Medicine·G J FisherJ J Voorhees
Feb 6, 1999·International Journal of Cancer. Journal International Du Cancer·C KuhnD F Spandau
Jul 27, 1999·Life Sciences·G Di CarloF Capasso
Feb 13, 2001·Biochemical and Biophysical Research Communications·Y Ibuki, R Goto
Nov 1, 2001·Annual Review of Cell and Developmental Biology·M D Sternlicht, Z Werb
Nov 17, 2001·The Journal of Investigative Dermatology·J H ChungH C Eun
Mar 1, 2002·Mechanisms of Ageing and Development·Gail Jenkins
Sep 5, 2002·Ageing Research Reviews·Laure Rittié, Gary J Fisher
Nov 20, 2002·Archives of Dermatology·Gary J FisherJohn J Voorhees
Dec 18, 2002·Annals of the New York Academy of Sciences·Peter BrenneisenKarin Scharffetter-Kochanek
Aug 14, 2003·Photodermatology, Photoimmunology & Photomedicine·Jin Ho Chung
Sep 3, 2003·Nature Reviews. Cancer·Derek L Stirewalt, Jerald P Radich
Feb 5, 2004·Molecular Cell·James GriffithKumkum Saxena
Mar 17, 2004·Toxicology and Applied Pharmacology·Yasuhiro Matsumura, Honnavara N Ananthaswamy
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexei A VaginGarib N Murshudov
Mar 16, 2006·Journal of Agricultural and Food Chemistry·Jin Hwan LeeKi Hun Park
Jun 18, 2009·Journal of Computer-aided Molecular Design·Lars NeumannDoris Hafenbradl
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Alexei Vagin, Alexei Teplyakov
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Dec 9, 2010·Nature Biotechnology·Mathias UhlenFredrik Ponten
Feb 18, 2011·Nature Reviews. Cancer·Ki Won LeeZigang Dong
Mar 13, 2012·Journal of the American Academy of Dermatology·Lucy ChenSteven Q Wang
Mar 14, 2012·Journal of Agricultural and Food Chemistry·Hee Young JeonSang-Jun Lee
Jul 25, 2012·Brain Research·Cibele Canal CastroCarlos Alexandre Netto
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Krysta BiniekReinhold H Dauskardt
Jan 26, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Camilla TaxvigChristine Nellemann
Oct 15, 2013·The Journal of Investigative Dermatology·Ellen H van den BogaardHans J P M Koenen

❮ Previous
Next ❯

Citations

Mar 23, 2017·International Journal of Molecular Sciences·Jieun ShinKi Won Lee
Oct 25, 2017·International Journal of Molecular Sciences·Jong-Eun KimKi Won Lee
Nov 19, 2017·The British Journal of Dermatology·S DingJ Huang
Nov 7, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Janine Beatriz Ramos AnastacioCarlos Alexandre Netto
Jul 2, 2020·Journal of Medicinal Food·Young-Ran SongTae-Gyu Lim
Apr 7, 2017·Biological & Pharmaceutical Bulletin·Jeong Ah HwangChang Seok Lee
Mar 31, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Prashamsa KoiralaJae Sue Choi
Jun 12, 2020·Journal of Microbiology and Biotechnology·Eun Hee JeongKi Won Lee
Jan 26, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Yun-Mi KangHyo-Jin An
Jan 21, 2021·International Journal of Molecular Sciences·Hadi MohsenpourMohammad Hosein Farzaei
Apr 20, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yanbei TuChengwei He
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giuseppe PaladiniRosanna Stancanelli

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.