Malorni W, Rivabene R, Straface E, Rainaldi G, Monti D, Salvioli S, Cossarizza A, Franceschi C
Dipartimento di Ultrastrutture, Istituto Superiore di Sanità, Rome, Italy.
Biochem Biophys Res Commun. 1995 Feb 15;207(2):715-24. doi: 10.1006/bbrc.1995.1246.
3-aminobenzamide (3-ABA) is an inhibitor of poly-(ADP-ribose)-polymerase, an enzyme involved in numerous subcellular processes, including cell death. Recently, a target effect of the drug on some cytoskeletal elements has also been described (Malorni et al., Biochem. Biophys. Res. Commun. 202: 915-922, 1994). In this study we evaluated the ability of 3-ABA to interfere with UV-B ray-induced apoptosis in cells selected for their cytoskeletal features and their different capability to adhere to the substrate. Human melanoma (M14) and epithelial (A431) cell lines and murine primary fibroblastic cultures (MFC) were studied. Our results indicate that cytoskeleton is indeed an important cellular target of 3-ABA, which can prevent apoptotic cell death by UV-B through a specific effect on the adhesion properties of the cells. Indeed, an inverse correlation was observed between sensitivity to UV-B-induced apoptosis (M14 > A431 > MFC) and substrate adhesion (MFC > A431 > M14). The potential relevance of these observations to understand the possible relationships among apoptosis, cytoskeletal functions and substrate adhesion is discussed.
3-氨基苯甲酰胺(3-ABA)是聚(ADP-核糖)聚合酶的抑制剂,该酶参与包括细胞死亡在内的众多亚细胞过程。最近,也有人描述了该药物对某些细胞骨架成分的靶向作用(马洛尼等人,《生物化学与生物物理研究通讯》202: 915 - 922,1994)。在本研究中,我们评估了3-ABA干扰紫外线B(UV-B)诱导细胞凋亡的能力,这些细胞因其细胞骨架特征以及附着于底物的不同能力而被挑选出来。我们研究了人黑色素瘤(M14)和上皮(A431)细胞系以及小鼠原代成纤维细胞培养物(MFC)。我们的结果表明,细胞骨架确实是3-ABA的一个重要细胞靶点,它可以通过对细胞黏附特性的特定作用来防止UV-B诱导的细胞凋亡。事实上,观察到对UV-B诱导凋亡的敏感性(M14 > A431 > MFC)与底物黏附(MFC > A431 > M14)之间呈负相关。本文讨论了这些观察结果对于理解凋亡、细胞骨架功能和底物黏附之间可能关系的潜在相关性。