脂蛋白是由脂質以及參與多功能的載脂蛋白所構成，例如：循環運輸、病毒顆粒製造以及壓力調節。DNA修復反應（DDR）的損傷已被證實會經由增加活性氧自由基（ROS）的製造，促進代謝失調並導致脂質代謝的改變。另外，C型肝炎病毒（HCV）感染也會增加細胞內ROS的製造以及損傷DDR，使得細胞更易於DNA突變。HCV不只引發病理性脂質累積，還會增進載脂蛋白J（apoJ）的表現，增加感染性HCV病毒顆粒的製造。此外，各種壓力例如：DNA損壞以及ROS，會引發細胞老化，使得細胞週期停滯。然而，脂質以及壓力誘導的載脂蛋白在DDR及細胞老化中是否扮演角色，目前仍不清楚。這裡我們假設：功能性脂質以及壓力誘導的載脂蛋白可能在健康的細胞中促成DDR以及細胞老化。結果顯示肝臟細胞對基因毒素的敏感度會受到HCV感染以及培養持續期間的影響。相同地，在輕微的氧化壓力或HCV急性感染之下，肝臟細胞表現嚴重的細胞老化，但此現象在慢性HCV感染時卻較輕微。這也許與細胞內ROS的清除能力有關，此處HCV急性感染相較於慢性感染有不同的細胞老化反應。此外，細胞內的總膽固醇及三酸甘油脂含量在感染後第137天有明顯的增加，但在此之後又減少了。另外，表現量增加的ApoJ與固醇醯基轉移酶2（SOAT2，一種將游離膽固醇轉變成膽固醇酯的內質網酵素）交互作用，並加強SOAT的活性去引發被HCV感染的細胞的病理性脂質累積。SOAT活性的抑制使得細胞存活率降低並增加細胞毒素誘導的細胞老化。總體而言，壓力誘導的載脂蛋白以及脂質可能在DDR、脂質累積及細胞老化扮演關鍵的角色。膽固醇及apoJ的恆定對於細胞調節細胞內的氧化壓力是必需要的。

Lipoproteins are comprised of lipids and apolipoproteins that participate in numerous functions such as circulatory transportation, viral particle production and stress regulation. It is evidenced that impaired DNA damage responses (DDR) promoted metabolic disorders and caused changes in lipid metabolism by increasing reactive oxygen species (ROS) production. In addition, hepatitis C virus (HCV) infection also increased intracellular ROS and impaired DDR, causing cells prone to DNA mutation. HCV not only induced pathological lipid accumulation but also increased the expression of apolipoprotein J (apoJ) to enhance infectious HCV particle production. Furthermore, various stresses such as DNA damage and ROS induced cellular senescence to pause cell cycle. However, it is still unknown whether lipids or stress-induced apolipoproteins play a role in DDR and cellular senescence. Here, we hypothesized that functional lipids and stress-induced apolipoproteins might contribute to DDR and cellular senescence in healthy cells. The results showed that sensitivity to genotoxins targeting base excision repair damage might be influenced by HCV infection and the cultivated duration of hepatocytes. Consistently, hepatocytes exhibited profound senescence under mild oxidative stress or with acute HCV infection, but mild in chronic HCV infection. These may be related to the ability of ROS clearance inside the cells, where HCV acute infection may have a distinct effect on cellular senescence response as compared to chronic infection. Moreover, intracellular total cholesterol and triglycerides levels were significantly increased until 137 days post infection, but decreased thereafter. In addition, the increasing level of apoJ interacted with SOAT2 (Sterol-O acyl transferase, an ER-associated enzyme that converted free cholesterol to cholesteryl ester) and enhanced SOAT activities to induce pathological lipid accumulation in HCV-infected cells. Inhibition of SOAT decreased cell viability and increased genotoxin-induced cellular senescence in hepatocytes. Together, stress-induced apolipoproteins and lipids might play crucial roles in DDR, lipid accumulation and cellular senescence. The maintenance of cholesterol and apoJ homeostasis might be necessary for the cells to regulate intracellular oxidative stress.

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