Ohno Yoshiya, Yagi Hideki, Nakamura Masanori, Masuko Kazue, Hashimoto Yoshiyuki, Masuko Takashi
Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502, Japan.
Biochem Biophys Res Commun. 2008 Mar 21;367(4):775-81. doi: 10.1016/j.bbrc.2008.01.030. Epub 2008 Jan 15.
Programmed cell death (PCD) is categorized as apoptotic, autophagic, or necrosis-like. Although the possibility that plural (two or three) death signals could be induced by a given stimulus has been reported, the precise mechanisms regulating PCD are not well understood. Recently, we have obtained two anti-chicken transferrin receptor (TfR) monoclonal antibodies (mAbs; D18 and D19) inducing a unique cell death. Although the cell death had several features of apoptosis, autophagic and necrosis-like morphological alterations were simultaneously observed in electron microphotographs. In addition to cells with condensed chromatin and an intact plasma membrane (apoptotic cells), cells having many vacuoles in the cytoplasm (autophagic cells), and enlarged cells with ruptured plasma membranes (necrosis-like cells) were observed in DT40 cells treated with the mAbs, however, the latter two types of dead cells were not detected upon treatment with staurosporine, a typical apoptosis inducer. In autophagic cells, numerous membrane-bound vesicles occupying most of the cytoplasmic space, which frequently contained electron-dense materials from cytoplasmic fragments and organelles, were observed. The simultaneous induction of multiple death signals from a stimulus via the TfR is of great interest to those researching cell death. In addition, activation of caspases was observed in DT40 cells treated with D19, however, the cell death was not inhibited with z-VAD-fmk, a pan-caspase inhibitor, suggesting that at least in part, a caspase-independent pathway is involved in the TfR-mediated cell death.
程序性细胞死亡（PCD）可分为凋亡性、自噬性或坏死样。尽管已有报道称给定刺激可能诱导多种（两种或三种）死亡信号，但调节PCD的精确机制仍未完全明了。最近，我们获得了两种抗鸡转铁蛋白受体（TfR）单克隆抗体（mAb；D18和D19），它们可诱导独特的细胞死亡。尽管这种细胞死亡具有凋亡的若干特征，但在电子显微镜照片中同时观察到了自噬性和坏死样的形态学改变。在用mAb处理的DT40细胞中，除了具有浓缩染色质和完整质膜的细胞（凋亡细胞）外，还观察到细胞质中有许多空泡的细胞（自噬细胞）以及质膜破裂的肿大细胞（坏死样细胞），然而，在用典型的凋亡诱导剂星形孢菌素处理时未检测到后两种类型的死亡细胞。在自噬细胞中，观察到大量膜结合囊泡占据了大部分细胞质空间，这些囊泡经常含有来自细胞质片段和细胞器的电子致密物质。通过TfR从刺激中同时诱导多种死亡信号，这对研究细胞死亡的人员来说非常有意义。此外，在用D19处理的DT40细胞中观察到了半胱天冬酶的激活，然而，细胞死亡并未被泛半胱天冬酶抑制剂z-VAD-fmk抑制，这表明至少部分地，一条不依赖半胱天冬酶的途径参与了TfR介导的细胞死亡。
