Sphingosine 1‐phosphate attenuates peroxide‐induced apoptosis in HaCaT cells cultured in vitro. (21st March 2013)

• Record Type: Journal Article
• Authors: Moriue, T.; Igarashi, J.; Yoneda, K.; Hashimoto, T.; Nakai, K.; Kosaka, H.; Kubota, Y.
• Is Part Of: Clinical and experimental dermatology. Volume 38:Number 6(2013)
• Page Start: 638
• Page End: 645
• Publication Date: 2013-03-21
• Subjects: Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/ced.12037
• Languages: English
• ISSNs: 0307-6938

Abstract

<abstract abstract-type="main" id="ced12037-abs-0001"> <title>Summary</title> <sec id="ced12037-sec-0001" sec-type="section"> <title>Background</title> <p>Sphingosine 1‐phosphate (S1P) is a sphingolipid mediator that elicits a wide array of physiological responses in various types of mammalian cells. Among the numerous biological activities elicited by S1P is protection from apoptotic cell death, which seems to take place through the cell‐surface S1P receptor and the downstream phosphoinositide 3′‐OH kinase (PI3‐K)/Akt pathway. It is unclear whether and how S1P protects human keratinocytes from hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)‐induced apoptosis.</p> </sec> <sec id="ced12037-sec-0002" sec-type="section"> <title>Aim</title> <p>We investigated the effects of S1P on apoptotic cell death in HaCaT cells, spontaneously immortalized human keratinocytes.</p> </sec> <sec id="ced12037-sec-0003" sec-type="section"> <title>Methods</title> <p>HaCaT cells were treated with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) 1–2 mmol/L as an inducer of apoptosis. Cellular apoptosis was assessed with terminal dUTP nick‐end labelling (TUNEL), WST‐8 and immunoblot assays.</p> </sec> <sec id="ced12037-sec-0004" sec-type="section"> <title>Results</title> <p>In WST‐8 and TUNEL assays, S1P pretreatment (1 μmol/L for 30 min) attenuated H<sub>2</sub>O<sub>2</sub>‐induced cell death. Promotion of the cleavage of caspase‐3 by H<sub>2</sub>O<sub>2</sub> was markedly attenuated when cells had been preincubated with S1P. S1P markedly potentiated phosphorylation (activation) of Akt in the presence of H<sub>2</sub>O<sub>2</sub>. Wortmannin, a selective inhibitor of the PI3‐K/Akt pathway, significantly suppressed S1P‐induced attenuation of caspase‐3 cleavage promoted by H<sub>2</sub>O<sub>2</sub>.</p> </sec> <sec id="ced12037-sec-0005" sec-type="section"> <title>Conclusions</title> <p>S1P, a sphingolipid mediator, attenuates H<sub>2</sub>O<sub>2</sub>‐induced apoptosis of HaCaT cells, by promoting phosphorylation of the Akt pathway.</p> </sec> </abstract>