Park Eun-Sook, Lee Jeong Hwa, Hong Ji Hye, Park Yong Kwang, Lee Joon Won, Lee Won-Jae, Lee Jae Won, Kim Kwang Pyo, Kim Kyun-Hwan
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea; KU Open Innovation Center, Konkuk University, Seoul, Korea.
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi, Korea.
PLoS One. 2014 Aug 7;9(8):e103955. doi: 10.1371/journal.pone.0103955. eCollection 2014.
In this study, we investigated whether hepatitis B virus (HBV) causes the alteration of lipid metabolism and composition during acute infection and liver regeneration in a mouse model. The liver controls lipid biogenesis and bile acid homeostasis. Infection of HBV causes various liver diseases and impairs liver regeneration. As there are very few reports available in the literature on lipid alterations by HBV infection or HBV-mediated liver injury, we have analyzed phospholipids that have important roles in liver regeneration by using matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) in the livers of HBV model mice. As a result, we identified different phosphatidylcholines (PCs) showing significant changes in their composition as well as cationized ion adduct formation in HBV-infected mouse livers which are associated with virus-mediated regeneration defects. To find the factor of altered PCs, the expression kinetics of enzymes was also examined that regulate PC biosynthesis during liver regeneration. It is noteworthy that the expression of choline-phosphate cytidylyltransferase A (PCYT1A) was significantly delayed in wild type HBV-expressing livers. Moreover, the amount of hepatic total PC was also significantly decreased in wt HBV-expressing mice. These results suggest that infection of HBV alters the composition of PCs which may involve in HBV-mediated regeneration defects and liver disease.
在本研究中，我们调查了乙型肝炎病毒（HBV）在小鼠模型的急性感染和肝脏再生过程中是否会导致脂质代谢和组成的改变。肝脏控制脂质生物合成和胆汁酸稳态。HBV感染会引发各种肝脏疾病并损害肝脏再生。由于文献中关于HBV感染或HBV介导的肝损伤导致脂质改变的报道非常少，我们通过基质辅助激光解吸/电离（MALDI）成像质谱（IMS）分析了在HBV模型小鼠肝脏中对肝脏再生起重要作用的磷脂。结果，我们在HBV感染的小鼠肝脏中鉴定出不同的磷脂酰胆碱（PCs），其组成以及阳离子化离子加合物形成有显著变化，这与病毒介导的再生缺陷有关。为了找到PCs改变的因素，我们还检测了在肝脏再生过程中调节PC生物合成的酶的表达动力学。值得注意的是，在表达野生型HBV的肝脏中，胆碱磷酸胞苷转移酶A（PCYT1A）的表达显著延迟。此外，表达野生型HBV的小鼠肝脏中总PC的量也显著减少。这些结果表明，HBV感染会改变PCs的组成，这可能与HBV介导的再生缺陷和肝脏疾病有关。
