Mitochondria‐Specific Mouse Gene Array and its Application in Toxicogenomics

V. Desai
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Abstract

In recent years, mitochondria have gained significant attention in toxicology because of their involvement in several drug-induced toxicities and in the pathogenesis of a number of degenerative diseases. Thus far, numerous molecular and biochemical assays have been developed and utilized to understand the association between mitochondria and drug toxicities or disease processes. However, the knowledge gained by these assays is inadequate to obtain a comprehensive outlook of the mitochondrial activity during toxic exposures and the underlying pathologies. High-throughput technologies, such as DNA microarray, have great potential in advancing genomic research in toxicology. This technology allows expression profiling of thousands of genes in a single experiment. Building on this technology, a mitochondria-specific mouse oligonucleotide microarray (MitoChip) was developed, which is described in this review. This review also discusses results generated using the MitoChip in studies that were designed to elucidate the molecular mechanisms of altered mitochondrial function induced by anti-HIV drugs (zidovudine and lamivudine) and a weight-loss dietary supplement (usnic acid) in mice. The results from these studies clearly demonstrate that the MitoChip is a valuable genomic tool and can help unravel the underlying molecular basis of impaired mitochondrial function in drug-induced toxicities. Keywords: anti-HIV drugs; gene expression profiles; mitochondria; MitoChip; mouse; usnic acid
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线粒体特异性小鼠基因阵列及其在毒物基因组学中的应用
近年来,线粒体在毒理学中引起了极大的关注,因为它们参与了几种药物诱导的毒性和许多退行性疾病的发病机制。到目前为止,已经开发了许多分子和生化分析方法,并用于了解线粒体与药物毒性或疾病过程之间的关系。然而,通过这些检测获得的知识不足以全面了解毒性暴露期间的线粒体活性和潜在病理。DNA微阵列等高通量技术在推进毒理学基因组研究方面具有巨大潜力。这项技术允许在一次实验中对数千个基因进行表达谱分析。在此基础上,研制了线粒体特异性小鼠寡核苷酸微阵列(MitoChip)。本综述还讨论了使用MitoChip在研究中产生的结果,这些研究旨在阐明抗hiv药物(齐多夫定和拉米夫定)和减肥膳食补充剂(usnic酸)诱导小鼠线粒体功能改变的分子机制。这些研究的结果清楚地表明,MitoChip是一种有价值的基因组工具,可以帮助揭示药物诱导毒性中线粒体功能受损的潜在分子基础。关键词:抗hiv药物;基因表达谱;线粒体;MitoChip;鼠标;地衣酸
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