کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7988 572 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The inhibition of death receptor mediated apoptosis through lysosome stabilization following internalization of carboxyfullerene nanoparticles
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
The inhibition of death receptor mediated apoptosis through lysosome stabilization following internalization of carboxyfullerene nanoparticles
چکیده انگلیسی

Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). It is well known that nanomaterials of water- soluble fullerene derivatives are potent antioxidants and help to prevent the overproduction of mitochondrial reactive oxygen species (ROS). However, whether their interaction with cells via the death receptor pathway is direct or indirect remains poorly understood. Here, we show that a bis-adduct malonic acid derivative of fullerene, C60(C(COOH)2)2, inhibits tumor necrosis factor alpha-initiated cellular apoptosis via stabilizing lysosomes. Data presented here demonstrate that nano-sized aggregates of this water-soluble fullerene derivative are endocytosed into cells and enriched in the lysosomes. During the internalization of C60(C(COOH)2)2, the expression of Hsp 70 is significantly upregulated, promoting cell survival by inhibiting the permeabilization of lysosomal membranes. In addition, the acidic environment inside lysosomes has a marked but temporary effect on the size distribution of fullerenic nanoparticles, and may disperse the aggregated C60(C(COOH)2)2 nanoparticles into single molecules or smaller aggregates. These single molecules or smaller aggregates may insert into the lysosomal membranes, further stabilizing them and decreasing the release of cathepsins from lysosomes, leading to the inhibition of tumor necrosis factor-induced apoptosis. C60(C(COOH)2)2 nanoparticles can thus protect cells by stabilizing lysosomal membranes via both upregulated expression of Hsp 70 and by their interactions with lysosomal membranes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 32, Issue 16, June 2011, Pages 4030–4041
نویسندگان
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