Department of Pediatrics, Division of Neurology, Hospital for Sick Children, University of Toronto, 555 University, Ave., Toronto, Ontario M5G 1X8, Canada; Genetics and Genome Biology Program, The Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Department of Pediatrics, Division of Neurology, Hospital for Sick Children, University of Toronto, 555 University, Ave., Toronto, Ontario M5G 1X8, Canada; Genetics and Genome Biology Program, The Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada.
Clin Chim Acta. 2020 Jun;505:92-97. doi: 10.1016/j.cca.2020.02.015. Epub 2020 Feb 15.
Carnitine is essential for long-chain fatty acid oxidation in muscle and heart. Tissue stores are regulated by organic cation/Cn transporter plasmalemmal Octn2. We previously demonstrated low carnitine in quadriceps/gluteus and heart of adult mdx mice.
We studied protein and mRNA expression of Octn2, mitochondrial Octn1 and peroxisomal Octn3 in adult male C57BL/10ScSn-DMD mdx/J quadriceps, heart, and diaphragm compared to C57BL/10SnJ mice.
We demonstrated reduction in mOctn2 expression on Western blot and similar expression of mOctn1 and mOctn3 in mdx quadriceps, heart and diaphragm. There was a significant upregulation of mOctn1 and mOctn2 mRNA by qRT-PCR in mdx quadriceps and of mOctn2 and mOctn3 mRNA in mdx heart. We showed upregulation of mdx mOctn1 and mOctn3 mRNA but no increase in protein expression.
Dystrophin deficiency likely disrupts Octn2 expression decreasing muscle carnitine uptake thus contributing to membranotoxic long-chain acyl-CoAs with sarcolemmal and organellar membrane oxidative injury providing a treatment rationale for early L-carnitine in DMD.
肉碱对于肌肉和心脏中的长链脂肪酸氧化至关重要。组织储存受有机阳离子/阳离子转运蛋白质膜 Octn2 调节。我们之前证明成年 mdx 小鼠的股四头肌/臀肌和心脏中的肉碱含量较低。
我们研究了成年雄性 C57BL/10ScSn-DMD mdx/J 股四头肌、心脏和膈肌中的 Octn2、线粒体 Octn1 和过氧化物酶体 Octn3 的蛋白和 mRNA 表达，与 C57BL/10SnJ 小鼠进行了比较。
我们通过 Western blot 证明 mOctn2 表达减少，mdx 股四头肌、心脏和膈肌中的 mOctn1 和 mOctn3 表达相似。mdx 股四头肌中的 mOctn1 和 mOctn2 mRNA 通过 qRT-PCR 显著上调，mdx 心脏中的 mOctn2 和 mOctn3 mRNA 上调。我们表明 mdx mOctn1 和 mOctn3 mRNA 上调，但蛋白表达没有增加。
肌营养不良蛋白缺乏可能会破坏 Octn2 的表达，从而减少肌肉肉碱的摄取，从而导致肌细胞膜毒性长链酰基辅酶 A，导致肌细胞膜和细胞器膜氧化损伤，为 DMD 中的早期 L-肉碱治疗提供了理论依据。
