HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by UMEDA, J. Articles by TAKEDA, J. Search for Related Content PubMed PubMed Citation Articles by UMEDA, J. Articles by TAKEDA, J.

In vivo cooperation between Bcl-x_L and the phosphoinositide 3-kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis

JIRO UMEDA, SHIGETOSHI SANO¹, KAZUHIKO KOGAWA, NOBORU MOTOYAMA, KUNIHIKO YOSHIKAWA, SATOSHI ITAMI, GEN KONDOH, TAKESHI WATANABE and JUNJI TAKEDA

Department of Dermatology,
Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and
Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan

¹Correspondence: Department of Dermatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Osaka 565-0871, Japan. E-mail: sano{at}derma.med.osaka-u.ac.jp

To investigate the function of Bcl-x_L in the skin, we established keratinocyte-specific Bcl-x gene-targeted mice under the keratin 5 promoter (K5). K5.Bcl-x_L-/- mice were viable, devoid of alteration in the development of skin or appendages. However, they harbored spontaneous apoptotic keratinocytes in the epidermis. Bcl-x_L-deficient keratinocytes cultured in vitro readily underwent apoptosis in the absence of growth factors, but the addition of HGF or EGF resulted in restoration of cell survival, which was reversed by treatment with wortmannin, an inhibitor of phosphoinositide-3 kinase (PI3K). Topical treatment of K5.Bcl-x_L-/- mice with wortmannin sensitized the skin for apoptosis induced by UV (UV) B, although wild-type epidermis was only marginally affected by this treatment, suggesting that the resistance to UVB largely depended on PI3K-Akt signaling in Bcl-x_L-deficient mice but not in wild-type mice. Furthermore, UVB irradiation resulted in redistribution of phosphorylated Akt from the basal layer to the suprabasal layer, indicating that Akt could spatially cooperate with Bcl-xL upon UVB exposure in the upper epidermis where Bcl-x_L is normally localized. These results suggest that Bcl-x_L and the PI3K-Akt pathway form a cooperative, intercompensatory axis for the protection of epidermal keratinocytes from apoptosis in vivo.—Umeda, J., Sano, S., Kogawa, K., Motoyama, N., Yoshikawa, K., Itami, S., Kondoh, G., Watanabe, T., Takeda, J. In vivo cooperation between Bcl-x_L and the phosphoinositide 3-kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis

Key Words: Cre-loxP • UVB irradiation • sunburn cells

This article has been cited by other articles:

				S. Aarabi, K. A. Bhatt, Y. Shi, J. Paterno, E. I. Chang, S. A. Loh, J. W. Holmes, M. T. Longaker, H. Yee, and G. C. Gurtner Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis FASEB J, October 1, 2007; 21(12): 3250 - 3261. [Abstract] [Full Text] [PDF]

				M. Iizuka, K. Sasaki, Y. Hirai, K. Shindo, S. Konno, H. Itou, S. Ohshima, Y. Horie, and S. Watanabe Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G39 - G52. [Abstract] [Full Text] [PDF]

				B. R. Thrash, C. W. Menges, R. H. Pierce, and D. J. McCance AKT1 Provides an Essential Survival Signal Required for Differentiation and Stratification of Primary Human Keratinocytes J. Biol. Chem., April 28, 2006; 281(17): 12155 - 12162. [Abstract] [Full Text] [PDF]

				J. H. Lee, D. Schutte, G. Wulf, L. Fuzesi, H.-J. Radzun, S. Schweyer, W. Engel, and K. Nayernia Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway Hum. Mol. Genet., January 15, 2006; 15(2): 201 - 211. [Abstract] [Full Text] [PDF]

				S. Sano, K. S. Chan, M. Kira, K. Kataoka, S. Takagi, M. Tarutani, S. Itami, K. Kiguchi, M. Yokoi, K. Sugasawa, et al. Signal Transducer and Activator of Transcription 3 Is a Key Regulator of Keratinocyte Survival and Proliferation following UV Irradiation Cancer Res., July 1, 2005; 65(13): 5720 - 5729. [Abstract] [Full Text] [PDF]

				M. A. Bachelor, S. J. Cooper, E. T. Sikorski, and G. T. Bowden Inhibition of p38 Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase Decreases UVB-Induced Activator Protein-1 and Cyclooxygenase-2 in a SKH-1 Hairless Mouse Model Mol. Cancer Res., February 1, 2005; 3(2): 90 - 99. [Abstract] [Full Text] [PDF]

				S. M. Janes, T. A. Ofstad, D. H. Campbell, F. M. Watt, and D. M. Prowse Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt J. Cell Sci., August 15, 2004; 117(18): 4157 - 4168. [Abstract] [Full Text] [PDF]

				B. Guilbault and R. J. Kay RasGRP1 Sensitizes an Immature B Cell Line to Antigen Receptor-induced Apoptosis J. Biol. Chem., May 7, 2004; 279(19): 19523 - 19530. [Abstract] [Full Text] [PDF]