Metallothionein protects against oxidative stress-induced lysosomal destabilization
Metallothionein protects against oxidative stress-induced lysosomal destabilization
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DOI：
10.1042/bj20051143
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发表时间：
2006-02-15
影响因子：
4.1
通讯作者：
Brunk, UT
中科院分区：
文献类型：
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作者：
Baird, SK;Kurz, T;Brunk, UT
将载铁蛋白或与淀粉结合的铁螯合剂DFO（去铁胺）引入溶酶体腔室，通过结合溶酶体内氧化铁，保护细胞免受氧化应激、溶酶体破裂和随后的凋亡/坏死，从而防止芬顿型反应和随后的溶酶体膜过氧化。由于MTs（金属硫蛋白）的上调也会增强细胞对氧化应激（包括x射线照射）的抵抗力，并且MTs被发现能够在所有酸性和还原溶酶体样环境中与铁结合，我们提出这些蛋白质可能类似地稳定溶酶体自噬递送到溶酶体室后的溶酶体。在这里，我们报告了锌介导的MT上调，通过Western blotting和免疫细胞化学检测，导致溶酶体稳定并减少氧化应激后的凋亡，类似于载铁蛋白或DFO的液相内吞作用所提供的保护。相反，磷酸铁复合物的内吞摄取会破坏溶酶体抗氧化应激的稳定性，但这在MT上调的细胞中被抑制。这表明，已知在MT丰富的细胞中发生的抗氧化应激能力可能是MT自噬转换的结果，导致铁催化的溶酶体内过氧化反应减少。
The introduction of apo-ferritin or the iron chelator DFO (desferrioxamine) Conjugated to starch into the lysosomal compartment protects cells against oxidative stress, lysosomal rupture and ensuing apoptosis/necrosis by binding intralysosomal redoxactive iron, thus preventing Fenton-type reactions and ensuing peroxidation of lysosomal membranes. Because Up-regulation of MTs (metallothioneins) also generates enhanced cellular resistance to oxidative stress, including X-irradiation, and MTs were found to be capable of iron binding in ail acidic and reducing lysosomal-like environment, we propose that these proteins might similarly stabilize lysosonies following autophagocytotic delivery to the lysosomal compartment. Here, we report that Zn-mediated MT up-regulation, assayed by Western blotting and immunocytochemistry, results in lysosomal stabilization and decreased apoptosis following oxidative stress, similar to the protection afforded by fluid-phase endocytosis of apo-ferritin or DFO. In contrast, the endocytotic uptake of an iron phosphate complex destabilized lysosomes against oxidative stress, but this was suppressed in cells With up-regulated MT. It is suggested that the resistance against oxidative stress, known to occur in MT-rich cells, may be a consequence of autophagic turnover of MT, resulting in reduced iron-catalysed intralysosomal peroxidative reactions.