Telbisz Agnes, Kovács Attila L, Somosy Zoltán
Fodor József National Center of Public Health National Frédéric Joliot-Curie Research Institute for Radiobiology and Radiohygiene, Department of Radiopathology, 1775 Budapest, Hungary.
Micron. 2002;33(2):143-51. doi: 10.1016/s0968-4328(01)00005-1.
Lysosomes have an important role in radiation injury of cells and tissues. Activation of autophagy is frequently observed in different types of pathological tissue degeneration. In radiation response it increases in some cases, and lysosomes are responsible for regulated degradation of the autophagic vacuoles. Lysosomes are also involved in ionizing radiation induced cell death. In apoptosis lysosomes degrade content of the phagocytotic vacuoles derived from engulfed apoptotic blebs. On the other hand lysosomal enzymes discharged from disintegrated cells have a key role in induction of necrotic changes. In this work we investigate autophagy and lysosomal protein degradation in the relatively radiation insensitive exocrine pancreatic acini in vivo and in vitro. Type of cell death induced by X-ray was also examined in relation to the changes of the lysosomal processes. In 5h after 16 Gy in vivo whole body irradiation we observed significant increase in the cytoplasmic volume fraction of autophagic vacuoles and in the number of apoptotic cells in vivo. But in the acini isolated from irradiated rats we could not detect a change in the lysosomal degradation of intracellular proteins. Therefore irradiation probably influences the autophagy in an earlier step than lysosomal degradation. Extended necrotic lesions were not observed in vivo as long as 48 h. Isolated pancreatic acini usually contain more autophagic vacuoles than in vivo, but we could not observe additional increase in autophagy after 8 Gy, in vitro irradiation. Lysosomal degradation of intracellular proteins was also unaltered after 8 Gy, in vitro irradiation. Other biochemical functional parameters of the isolated pancreatic acini, like protein synthesis and amylase secretion were not changed either after 8 Gy, in vitro X-ray treatment. These results indicate that pancreatic acinar cells in vitro have a high tolerance to irradiation. The observed in vivo radiation induced changes of the exocrine pancreas are possibly indirectly induced by injuries of more sensitive mechanisms.
溶酶体在细胞和组织的辐射损伤中起重要作用。自噬激活常见于不同类型的病理性组织退化。在辐射反应中，自噬在某些情况下会增强，溶酶体负责自噬空泡的调控性降解。溶酶体也参与电离辐射诱导的细胞死亡。在细胞凋亡过程中，溶酶体降解源自吞噬凋亡小泡的吞噬空泡内容物。另一方面，从解体细胞中释放的溶酶体酶在坏死变化的诱导中起关键作用。在这项工作中，我们研究了体内和体外相对辐射不敏感的外分泌胰腺腺泡中的自噬和溶酶体蛋白降解。还研究了X射线诱导的细胞死亡类型与溶酶体过程变化的关系。在体内全身照射16 Gy后5小时，我们观察到体内自噬空泡的细胞质体积分数和凋亡细胞数量显著增加。但在从受照射大鼠分离的腺泡中，我们未检测到细胞内蛋白质溶酶体降解的变化。因此，辐射可能在比溶酶体降解更早的步骤影响自噬。长达48小时在体内未观察到广泛的坏死病变。分离的胰腺腺泡通常比体内含有更多的自噬空泡，但在体外照射8 Gy后，我们未观察到自噬的额外增加。体外照射8 Gy后，细胞内蛋白质的溶酶体降解也未改变。体外X射线处理8 Gy后，分离的胰腺腺泡的其他生化功能参数，如蛋白质合成和淀粉酶分泌也未改变。这些结果表明体外胰腺腺泡细胞对辐射具有高耐受性。观察到的体内辐射诱导的外分泌胰腺变化可能是由更敏感机制的损伤间接诱导的。
