Hefei National Laboratory for Physical Sciences at Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, People's Republic of China.
Nanotechnology. 2013 Apr 26;24(16):165102. doi: 10.1088/0957-4484/24/16/165102. Epub 2013 Mar 27.
A variety of inorganic nanomaterials have been shown to induce autophagy, a cellular degradation process critical for the maintenance of cellular homeostasis. The overwhelming majority of autophagic responses elicited by nanomaterials were detrimental to cell fate and contributed to increased cell death. A widely held view is that the inorganic nanoparticles, when encapsulated and trapped by autophagosomes, may compromise the normal autophagic process due to the inability of the cells to degrade these materials and thus they manifest a detrimental effect on the well-being of a cell. Here we show that, contrary to this notion, nano-sized paramontroseite VO2 nanocrystals (P-VO2) induced cyto-protective, rather than death-promoting, autophagy in cultured HeLa cells. P-VO2 also caused up-regulation of heme oxygenase-1 (HO-1), a cellular protein with a demonstrated role in protecting cells against death under stress situations. The autophagy inhibitor 3-methyladenine significantly inhibited HO-1 up-regulation and increased the rate of cell death in cells treated with P-VO2, while the HO-1 inhibitor protoporphyrin IX zinc (II) (ZnPP) enhanced the occurrence of cell death in the P-VO2-treated cells while having no effect on the autophagic response induced by P-VO2. On the other hand, Y2O3 nanocrystals, a control nanomaterial, induced death-promoting autophagy without affecting the level of expression of HO-1, and the pro-death effect of the autophagy induced by Y2O3. Our results represent the first report on a novel nanomaterial-induced cyto-protective autophagy, probably through up-regulation of HO-1, and may point to new possibilities for exploiting nanomaterial-induced autophagy for therapeutic applications.
多种无机纳米材料已被证明能诱导自噬，这是一种对维持细胞内稳态至关重要的细胞降解过程。绝大多数纳米材料引发的自噬反应对细胞命运都是有害的，并导致细胞死亡增加。一种广泛持有的观点认为，当无机纳米颗粒被自噬体包裹和捕获时，由于细胞无法降解这些物质，可能会破坏正常的自噬过程，因此它们对细胞的健康表现出有害影响。在这里，我们表明，与这一观点相反，纳米尺寸的斜方辉石 VO2 纳米晶体（P-VO2）在培养的 HeLa 细胞中诱导细胞保护性的、而非促进死亡的自噬。P-VO2 还引起血红素加氧酶-1（HO-1）的上调，HO-1 是一种在应激条件下保护细胞免受死亡的细胞蛋白。自噬抑制剂 3-甲基腺嘌呤显著抑制了 HO-1 的上调，并增加了用 P-VO2 处理的细胞中的细胞死亡率，而 HO-1 抑制剂原卟啉 IX 锌（II）（ZnPP）增强了 P-VO2 处理的细胞中的细胞死亡的发生，而对 P-VO2 诱导的自噬反应没有影响。另一方面，Y2O3 纳米晶体，一种对照纳米材料，诱导促进死亡的自噬，而不影响 HO-1 的表达水平，以及 Y2O3 诱导的自噬的促死亡作用。我们的结果代表了首例关于新型纳米材料诱导的细胞保护性自噬的报告，可能是通过上调 HO-1，这可能为利用纳米材料诱导的自噬进行治疗应用开辟新的可能性。
