Bulteau Anne-Laure, Moreau Marielle, Nizard Carine, Friguet Bertrand
Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, Université Paris 7-Denis Diderot, 2 Place Jussieu, 75251, Paris Cedex 05, France.
Ann N Y Acad Sci. 2007 Apr;1100:280-90. doi: 10.1196/annals.1395.029.
Cellular aging is characterized by the accumulation of oxidatively modified proteins that result, at least in part, from impaired degradation of abnormal proteins. The proteasome is the major intracellular proteolytic system implicated in the removal of abnormal and oxidized proteins. In human epidermal cells, previous studies have evidenced that proteasome function is decreased during aging as well as upon UV irradiation, which is the main component of photoaging. The age-related decline of proteasome activity has been reported to be due to either or both decreased proteasome subunits expression and content, inactivation upon alteration of proteasome subunits, and accumulation of endogenous inhibitors, such as highly oxidized and cross-linked proteins. To gain further insight in the mechanisms that might be implicated in the decreased activity of the proteasome upon photoaging, purified 20S human proteasome has been exposed to UVA- and UVB-irradiation. The effect of such an irradiation on proteasome peptidase activities has been monitored and shown to promote a stimulation or an inhibition of the peptidase activities depending on whether the proteasome is under its latent or a nonphysiological active form. Analysis of the patterns of proteasome subunits by 2D gel electrophoresis has revealed modification for several subunits for UV-irradiated proteasome only in its irreversibly activated form, compared with nonirradiated and irradiated latent forms, indicating that the 20S proteasome is rather resistant to UV irradiation.
细胞衰老的特征是氧化修饰蛋白的积累，这至少部分是由于异常蛋白降解受损所致。蛋白酶体是参与清除异常和氧化蛋白的主要细胞内蛋白水解系统。在人类表皮细胞中，先前的研究表明，在衰老过程以及紫外线照射（光老化的主要成分）后，蛋白酶体功能会下降。据报道，与年龄相关的蛋白酶体活性下降是由于蛋白酶体亚基表达和含量降低、蛋白酶体亚基改变导致失活以及内源性抑制剂（如高度氧化和交联的蛋白质）积累中的一种或两种原因。为了进一步深入了解光老化时蛋白酶体活性降低可能涉及的机制，已将纯化的20S人蛋白酶体暴露于UVA和UVB照射下。已监测了这种照射对蛋白酶体肽酶活性的影响，结果表明，根据蛋白酶体处于潜在形式还是非生理活性形式，这种照射会促进肽酶活性的刺激或抑制。通过二维凝胶电泳分析蛋白酶体亚基的模式发现，与未照射和照射后的潜在形式相比，紫外线照射后的蛋白酶体仅在其不可逆激活形式下有几个亚基发生了修饰，这表明20S蛋白酶体对紫外线照射具有相当的抗性。
