Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy
Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy
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DOI：
10.1016/s0006-2952(98)00055-0
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发表时间：
1998-09-15
影响因子：
5.8
通讯作者：
Polla, BS
中科院分区：
文献类型：
--
作者：
Bornman, L;Rossouw, H;Polla, BS
杜氏肌营养不良症（DMD）是由肌营养不良蛋白缺乏引起的，其导致肌肉坏死和热休克/应激蛋白（HSP）的上调。我们假设活性氧，特别是羟基自由基（（OH）-O-），参与肌肉坏死和HSP表达。据推测，铁剥夺减少（OH）-O-。抑制疾病进程，减少氧化剂诱导的HSP表达。在Duchenne型肌营养不良症（mdx）小鼠模型中，通过检查饮食缺乏和补充铁对维持饮食缺乏或补充铁6周的小鼠的血清肌酸激酶（CK）、肌肉形态学、脂质过氧化和HSP水平的影响，评价铁催化的自由基反应在肌营养不良蛋白缺乏的肌肉病理学中的作用。铁剥夺mdx小鼠表现出显着减少巨噬细胞侵入坏死纤维的数量和70 kDa的热休克蛋白（Hsp 70）的表达。这表明铁依赖性的（OH）-O-的产生。与mdx小鼠的肌肉坏死有关，并在体内调节Hsp 70的表达。与此相反，铁剥夺没有影响其他HSP或脂质过氧化作用的mdx小鼠，而维持任何饮食引起血清肌酸激酶活性显着下降。铁剥夺对mdx的潜在治疗作用应予以考虑。(C)1998年爱思唯尔科学公司
Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency, which results in muscle necrosis and the upregulation of heat shock/stress proteins (HSP). We hypothesized that reactive oxygen species, and in particular hydroxyl radicals ((OH)-O-.), participate in muscle necrosis and HSP expression. It was assumed that iron deprivation decreases (OH)-O-. generation, restraining the disease process and reducing the oxidant-induced expression of HSP. The role of iron-catalyzed free radical reactions in the pathology of dystrophin-deficient muscle was evaluated in the murine model for Duchenne muscular dystrophy (mdx), by examining the effects of dietary deficiency and supplementation of iron on serum creatine kinase (CK), muscle morphology, lipid peroxidation and HSP levels in mice maintained on diets deficient in or supplemented with iron for 6 weeks. Iron-deprived mdx mice showed a significant decrease in the number of macrophage-invaded necrotic fibers and the expression of the 70-kDa heat shock protein (Hsp70). This suggests that the iron-dependent generation of (OH)-O-. relates to muscle necrosis in the mdx mouse and modulates the expression of Hsp70 in vivo. In contrast, iron deprivation had no influence on other HSP or on lipid peroxidation in mdx mice, while maintenance on either diet caused a significant decrease in serum creatine kinase activity. The potential therapeutic effects of iron deprivation in mdx should be considered. (C) 1998 Elsevier Science Inc.