Ultraviolet-B radiation causes an upregulation of survivin in human keratinocytes and mouse skin.
Understanding of the mechanism of ultraviolet (UV)-mediated cutaneous damages is far from complete. The cancer-specific expression of Survivin, a member of the inhibitor of apoptosis family of proteins, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a target for cancer treatment. This study was designed to investigate the modulation of Survivin during UV response, both in vitro and in vivo. We used UV-B-mediated damages in normal human epidermal keratinocytes (NHEK) cells as an in vitro model and SKH-1 hairless mouse model for the in vivo studies. For in vitro studies, NHEK were treated with UV-B and samples were processed at 5, 15, 30 min, 1, 3, 6, 12 and 24 h after treatment. Our data demonstrated that UV-B exposure (50 mJ/cm2) to NHEK resulted in a significant upregulation in Survivin messenger RNA (mRNA) and protein levels. We also observed that UV-B exposure to NHEK resulted in significant (1) decrease in Smac/DIABLO and (2) increase in p53. For in vivo studies, the SKH-1 hairless mice were subjected to a single exposure of UV-B (180 mJ/cm2), and samples were processed at 3, 6, 12 and 24 h after UV-B exposure. UV-B treatment resulted in a significant increase in protein or mRNA levels (or both) of Survivin, phospho-Survivin and p53 and a concomitant decrease in Smac/DIABLO in mouse skin. This study demonstrated, for the first time, the involvement of Survivin (and the associated events) in UV-B response in vitro and in vivo in experimental models regarded to have relevance to human situations.
Aziz
Moammir Hasan
MH
Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.
Ghotra
Amaninderapal S
AS
Shukla
Yogeshwer
Y
Ahmad
Nihal
N
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D015536:Down-Regulation / Q000528:radiation effects; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010769:Phosphothreonine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects*
D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D010769:Phosphothreonine