Anand Sanjay, Chakrabarti Enakshi, Kawamura Hiroko, Taylor Charles R, Maytin Edward V
Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Invest Dermatol. 2005 Aug;125(2):323-33. doi: 10.1111/j.0022-202X.2005.23784.x.
C/EBP-homologous protein (CHOP)/gadd153 (or CHOP) is a transcription factor induced by endoplasmic reticulum (ER) stress. Forcible overexpression of CHOP causes apoptosis in keratinocytes in culture. Here, we asked whether CHOP might be increased in the skin after UVB (280-320 nm) exposure, thus implicating CHOP in sunburn cell (SBC) formation. SKH-1 hairless mice were exposed to a ultraviolet (UV) source (80 mJ per cm2; approximately 74% UVB, approximately 16% UVA), and skin biopsies examined by immunohistology and immunoprecipitation. Compared with non-irradiated epidermis, CHOP expression was significantly increased at 30 min, and reached maximal levels by 24 h. Similar increases in CHOP following UVB exposure were observed in human buttock skin. The time course of CHOP expression preceded SBC formation and another marker of apoptosis, caspase-3 cleavage. Intracellular CHOP accumulated mainly in cytoplasmic and perinuclear locations, with little remaining in the nucleus. To examine mechanisms, cultured keratinocytes were irradiated in vitro and examined by western blotting. Under conditions that eliminated ER stress because of cell handling, CHOP did not accumulate (and was in fact decreased) in the cells. Thus, induction of CHOP in keratinocytes requires factors present only in the native skin. Overall, the data suggest that CHOP participates in adaptive responses of the epidermis following UVB/UVA exposure in vivo.
C/EBP 同源蛋白（CHOP）/gadd153（或 CHOP）是一种由内质网（ER）应激诱导产生的转录因子。在培养的角质形成细胞中，强制过表达 CHOP 会导致细胞凋亡。在此，我们探究了在紫外线 B（UVB，280 - 320 纳米）照射后，皮肤中 CHOP 的表达是否会增加，从而表明 CHOP 与晒伤细胞（SBC）的形成有关。将 SKH - 1 无毛小鼠暴露于紫外线光源（每平方厘米 80 毫焦；约 74% UVB，约 16% UVA）下，通过免疫组织学和免疫沉淀法对皮肤活检样本进行检测。与未照射的表皮相比，CHOP 的表达在 30 分钟时显著增加，并在 24 小时时达到最高水平。在人类臀部皮肤中也观察到 UVB 照射后 CHOP 有类似的增加情况。CHOP 表达的时间进程先于 SBC 的形成以及另一个凋亡标志物——半胱天冬酶 - 3 的裂解。细胞内的 CHOP 主要积聚在细胞质和核周区域，细胞核中残留较少。为了探究其机制，对体外培养的角质形成细胞进行照射，并通过蛋白质印迹法进行检测。在因细胞操作而消除 ER 应激的条件下，细胞中 CHOP 并未积聚（实际上是减少的）。因此，角质形成细胞中 CHOP 的诱导需要仅存在于天然皮肤中的因子。总体而言，数据表明 CHOP 参与了体内 UVB/UVA 照射后表皮的适应性反应。
