Kim Kyoung Hwan, Park Jeong-Woong, Yang Young Mok, Song Ki-Duk, Cho Byung-Wook
Department of Animal Science, College of Natural Resources and Life Sciences, Pusan National University, Miryang 50463, Korea.
Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Korea.
Anim Biosci. 2021 Feb;34(2):312-319. doi: 10.5713/ajas.20.0061. Epub 2020 Aug 24.
Stress-induced cytotoxicity caused by xenobiotics and endogenous metabolites induces the production of reactive oxygen species and often results in damage to cellular components such as DNA, proteins, and lipids. The cytochrome P450 (CYP) family of enzymes are most abundant in hepatocytes, where they play key roles in regulating cellular stress responses. We aimed to determine the effects of the antioxidant compound, methylsulfonylmethane (MSM), on oxidative stress response, and study the cytochrome P450 family 3 subfamily A (CYP3A) gene expression in fetal horse hepatocytes.
The expression of hepatocyte markers and CYP3A family genes (CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, and CYP3A97) were assessed in different organ tissues of the horse and fetal horse liver-derived cells (FHLCs) using quantitative reverse transcription polymerase chain reaction. To elucidate the antioxidant effects of MSM on FHLCs, cell viability, levels of oxidative markers, and gene expression of CYP3A were investigated in H2O2-induced oxidative stress in the presence and absence of MSM.
FHLCs exhibited features of liver cells and simultaneously maintained the typical genetic characteristics of normal liver tissue; however, the expression profiles of some liver markers and CYP3A genes, except that of CYP3A93, were different. The expression of CYP3A93 specifically increased after the addition of H2O2 to the culture medium. MSM treatment reduced oxidative stress as well as the expression of CYP3A93 and heme oxygenase 1, an oxidative marker in FHLCs.
MSM could reduce oxidative stress and hepatotoxicity in FHLCs by altering CYP3A93 expression and related signaling pathways.
由外源性物质和内源性代谢产物引起的应激诱导细胞毒性会诱导活性氧的产生，并常常导致细胞成分如DNA、蛋白质和脂质的损伤。细胞色素P450（CYP）酶家族在肝细胞中最为丰富，它们在调节细胞应激反应中起关键作用。我们旨在确定抗氧化化合物甲磺酰甲烷（MSM）对氧化应激反应的影响，并研究马胎儿肝细胞中细胞色素P450家族3亚家族A（CYP3A）基因的表达。
使用定量逆转录聚合酶链反应评估马的不同器官组织和马胎儿肝脏来源细胞（FHLCs）中肝细胞标志物和CYP3A家族基因（CYP3A89、CYP3A93、CYP3A94、CYP3A95、CYP3A96和CYP3A97）的表达。为了阐明MSM对FHLCs的抗氧化作用，在有和没有MSM的情况下，研究了H2O2诱导的氧化应激中FHLCs的细胞活力、氧化标志物水平和CYP3A的基因表达。
FHLCs表现出肝细胞的特征，同时保持正常肝组织的典型遗传特征；然而，除CYP3A93外，一些肝脏标志物和CYP3A基因的表达谱有所不同。向培养基中添加H2O2后，CYP3A93的表达特异性增加。MSM处理降低了氧化应激以及FHLCs中CYP3A93和血红素加氧酶1（一种氧化标志物）的表达。
MSM可通过改变CYP3A93表达和相关信号通路来降低FHLCs中的氧化应激和肝毒性。
