Cited 19 times in

K6PC-5, a sphingosine kinase activator, induces anti-aging effects in intrinsically aged skin through intracellular Ca2+ signaling

Authors
 Jong-Kyung Youm  ;  Hae Jo  ;  Jeong Hee Hong  ;  Dong Min Shin  ;  Mi Jung Kwon  ;  Se Kyoo Jeong  ;  Byeong Deog Park  ;  Eung Ho Choi  ;  Seung Hun Lee 
Citation
 JOURNAL OF DERMATOLOGICAL SCIENCE, Vol.51(2) : 89-102, 2008 
Journal Title
JOURNAL OF DERMATOLOGICAL SCIENCE
ISSN
 0923-1811 
Issue Date
2008
MeSH
Aging/drug effects* ; Aging/metabolism ; Amides/pharmacology* ; Animals ; Calcium/metabolism ; Calcium Signaling/drug effects* ; Calcium Signaling/physiology ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Humans ; Lysophospholipids/antagonists & inhibitors ; Lysophospholipids/metabolism ; Male ; Mice ; Mice, Hairless ; Models, Animal ; Phosphotransferases (Alcohol Group Acceptor)/metabolism* ; Procollagen/metabolism ; Skin/cytology ; Skin/drug effects ; Skin/metabolism* ; Sphingosine/analogs & derivatives ; Sphingosine/antagonists & inhibitors ; Sphingosine/metabolism
Keywords
Sphingosine kinase ; Sphingosine-1-phosphate ; Ca2+ signaling ; Fibroblast proliferation ; Skin anti-aging
Abstract
BACKGROUND: Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, regulates multiple cellular responses such as Ca(2+) signaling, growth, survival, and differentiation. Because sphingosine kinase (SK) is the enzyme directly responsible for the production of S1P, many factors have been identified that regulate its activity and subsequent S1P levels. To date, there are no reports to demonstrate a chemically induced, direct activation of SK.

OBJECTIVE: Here we have studied the effects of K6PC-5 as a newly synthesized SK activator on fibroblast proliferation in both human fibroblasts and aged mouse skin. To demonstrate that K6PC-5 has S1P-mediated action mechanism in fibroblasts, we have measured SK-dependent intracellular Ca(2+) signaling.

METHODS: Fibroblasts were cultured primarily from human foreskin and were used to study the effect of K6PC-5 and S1P on intracellular Ca(2+) signaling and fibroblast proliferation. Changes in intracellular Ca(2+) were detected by fluorescence with fura-2/AM. To study skin anti-aging effects of K6PC-5, we used intrinsically aged hairless mice (56 weeks old).

RESULTS: K6PC-5 promoted fibroblast proliferation and procollagen production in human fibroblasts significantly. K6PC-5 induced intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations in human fibroblasts. Both dimethylsphingosine and dihydroxysphingosine, SK inhibitors, and the transfection of SK1-siRNA blocked the K6PC-5-induced increases in [Ca(2+)](i), an effect independent of the classical PLC/IP(3)-mediated pathway. The K6PC-5-induced [Ca(2+)](i) oscillations were dependent on thapsigargin-sensitive Ca(2+) stores and Ca(2+) entry. Topical application of K6PC-5 for 2 weeks to intrinsically aged hairless mice enhanced fibroblast proliferation, collagen production, and eventually increased dermal thickness (10%). K6PC-5 also promoted specific epidermal differentiation marker proteins, including involucrin, loricrin, filaggrin, and keratin 5, without any alterations on epidermal barrier function.

CONCLUSION: These results suggest that K6PC-5 acts to regulate fibroblast proliferation through intracellular S1P production, and can further promote keratinocyte differentiation. We anticipate that the regulation of S1P levels may represent a novel approach for the treatment of skin disorders, including skin aging.
Full Text
http://www.sciencedirect.com/science/article/pii/S0923181108000832
DOI
10.1016/j.jdermsci.2008.03.002
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Lee, Seung Hun(이승헌)
Jo, Hae(조해)
Hong, Jeong Hee(홍정희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106230
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links