TARGETED MS FOR DETECTION OF LIVER ENZYMES IN FATTY LIVER DISEASE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目前的肝功能测试（LFT）测量肝酶，如丙氨酸和天冬氨酸转氨酶，或ALT和AST，并被视为肝脏健康的线索。然而，确认和分期肝脏疾病的唯一方法是活检。除非有其他原因怀疑肝脏疾病，否则很少进行活检，疾病可能在可能逆转的时候未被诊断出来。 肝酶和其他蛋白质存在于血液中，这是由于细胞质从病变细胞和细胞凋亡中渗漏。细胞溶质蛋白质组的差异分析提供了额外的血清生物标志物候选者和深入了解疾病机制。使用酒精性脂肪性肝炎的胃内动物模型和细胞分级结合代谢标记，我已经确定了ALT，AST和其他潜在的有趣的血清诊断目标。此外，我提出了一种通过质谱法定量这些蛋白质的方法。通过分析正常和患病的血液样本，我可以开发一种更具体和准确的工具来诊断和潜在的肝病分期。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Current liver function tests (LFTs), measure liver enzymes such as alanine and aspartate aminotransferases, or ALT and AST, and are regarded as a clue to liver health. However, the only way to confirm and stage liver disease is biopsy. Unless there are other reasons to suspect liver disease, biopsies are rarely performed and disease may go undiagnosed at a time when it may be reversed. Liver enzymes and other proteins are present in the blood due to leakage of cytosol from diseased cells and apoptosis. Differential analysis of the cytosolic proteome provides additional serum bio-marker candidates and insight into disease mechanism. Using an intragastric animal model of alcoholic steatohepatitis and cell fractionation coupled to metabolic labeling, I have identified both ALT, AST, and other potentially interesting targets for serum diagnostics. Additionally, I present a method for quantifying these proteins by mass spectrometry. By analyzing normal and diseased blood samples, I can develop a more specific and accurate tool for diagnosing and potentially staging liver disease.