ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB.
Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-L(alpha), an upstream signaling molecule of ER stress, decreased at 1-4h after 10 mJ/cm(2) irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm(2) UVB at 4h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.
Mera
Kentaro
K
Department of Dermatology, Field of Sensory Organology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Kawahara
Ko-ichi
K
Tada
Ko-ichi
K
Kawai
Kazuhiro
K
Hashiguchi
Teruto
T
Maruyama
Ikuro
I
Kanekura
Takuro
T
D051702:Activating Transcription Factor 6 / Q000378:metabolism / Q000528:radiation effects; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000528:radiation effects; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000528:radiation effects*; D004722:Endoribonucleases / Q000378:metabolism / Q000528:radiation effects; D004781:Environmental Exposure; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D008565:Membrane Proteins / Q000378:metabolism / Q000528:radiation effects; D017510:Protein Folding / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000528:radiation effects; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction / Q000528:radiation effects; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism / Q000528:radiation effects; D054875:Ubiquitination; D014466:Ultraviolet Rays; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase / Q000378:metabolism
D051702:Activating Transcription Factor 6; D004268:DNA-Binding Proteins; D004722:Endoribonucleases; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase; C497111:ATF6 protein, human; C000605543:XBP1 protein, human; C403982:ERN2 protein, human