Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Int J Nanomedicine. 2010 Sep 7;5:601-9. doi: 10.2147/IJN.S11513.
Four rare earth oxides have been shown to induce autophagy. Interestingly, we often noticed plentiful vacuolization, which was not always involved in this autophagic process. In this study, we investigated three other rare-earth elements, including Yttrium (Y), Ytterbium (Yb), and Lanthanum (La). Autophagic effect could be induced by all of them but only Y(2)O(3) and Yb(2)O(3) could cause massive vacuolization. Y(2)O(3) and Yb(2)O(3) treated by sonication or centrifugation to reduce particle size were used to test vacuolization level in HeLa cell lines. The results showed that rare earth oxides-induced vacuolization is size-dependent and differs from autophagic pathway. To further clarify the characteristics of this autophagic process, we used MEF Atg-5 (autophagy associated gene 5) knockout cell line, and the result showed that the autophagic process induced by rare earth oxides is Atg-5-dependent and the observed vacuolization was independent from autophagy. Similar results could also be observed in our tests on 3-methyladenine(3-MA), a well-known autophagy inhibitor. In conclusion, for the first time, we clarified the relationship between massive vacuolization and autophagic process induced by rare earth oxides and pointed out the size effect of rare earth oxides on the formation of vacuoles, which give clues to further investigation on the mechanisms underlying their biological effects.
四种稀土氧化物已被证明能诱导自噬。有趣的是，我们经常观察到大量的空泡化，但这并不总是涉及自噬过程。在这项研究中，我们研究了另外三种稀土元素，包括钇（Y）、镱（Yb）和镧（La）。它们都能诱导自噬效应，但只有 Y2O3 和 Yb2O3 能引起大量的空泡化。我们用超声处理或离心来减小粒径的 Y2O3 和 Yb2O3 来测试 HeLa 细胞系中的空泡化水平。结果表明，稀土氧化物诱导的空泡化是尺寸依赖性的，与自噬途径不同。为了进一步阐明这种自噬过程的特征，我们使用了 MEF Atg-5（自噬相关基因 5）敲除细胞系，结果表明，稀土氧化物诱导的自噬过程是 Atg-5 依赖性的，观察到的空泡化与自噬无关。在我们对 3-甲基腺嘌呤（3-MA）的测试中也观察到了类似的结果，3-MA 是一种众所周知的自噬抑制剂。总之，我们首次阐明了稀土氧化物诱导的大量空泡化与自噬过程之间的关系，并指出了稀土氧化物对形成空泡的尺寸效应，这为进一步研究它们的生物学效应的机制提供了线索。
