Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and lipogenesis.
Knockout of SOD1 alters murine hepatic glycolysis, gluconeogenesis, and lipogenesis.
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DOI：
10.1016/j.freeradbiomed.2012.08.570
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发表时间：
2012-11-01
影响因子：
7.4
通讯作者：
Lei, Xin Gen
中科院分区：
文献类型：
--
作者：
Wang, Li;Jiang, Zongyong;Lei, Xin Gen
我们先前观察到敲除铜锌超氧化物歧化酶（SOD 1）比敲除硒依赖的谷胱甘肽过氧化物酶-1（GPX 1）对小鼠体重和葡萄糖稳态的影响更强。进行了两个实验，以确定肝脏脂质谱和关键代谢调节剂如何证实这种差异。向SOD 1 −/−、GPX 1 −/−及其相应野生型（WT）同窝仔（n = 6或7只/组，雄性）喂食硒充足的Torula酵母-蔗糖饲料，并在6月龄时处死以收集肝脏样本。在Exp. 1，与WT同窝仔相比，禁食SOD 1 −/−小鼠表现出丙酮酸不耐受和肝糖原减少61%（P < 0.05）。前者肝脏中磷酸烯醇式丙酮酸羧激酶、总蛋白磷酸酶和蛋白磷酸酶2A活性显著低于后者（P < 0.05），而葡萄糖激酶活性显著高于后者（P <0.05）。相反，在SOD 1 −/−小鼠中，总胆固醇、甘油三酯和非酯化脂肪酸的肝脏浓度增加了11%至100%（P < 0.05）。同时，这些小鼠的肝蛋白中固醇调节元件结合蛋白-1和2、p53 MAPK、总AMP活化蛋白激酶α 1蛋白和磷酸化AMP活化蛋白激酶α1蛋白、蛋白酪氨酸磷酸酶-1B和蛋白磷酸酶-2B水平升高（P < 0.05）。在Exp. 2，GPX 1-/-和它们的WT同窝仔进行了比较，但在任何测量中均未显示出差异。总之，敲除SOD 1，而不是GPX 1，导致减少肝糖原储存与丙酮酸不耐受和升高的肝脏脂质谱在成年小鼠同步。这种惊人的比较可能是由于这两种基因敲除对H2 O2细胞内张力和肝糖原异生、糖酵解和脂肪生成的关键调节因子的独特影响。
We previously observed a stronger effect of knockout of Cu, Zn superoxide dismutase (SOD1) than that of Se-dependent glutathione peroxidase-1(GPX1) on murine body weight and glucose homeostasis. Two experiments were conducted to determine how hepatic lipid profile and key metabolic regulators were corroborated with this difference. The SOD1−/−, GPX1−/−, and their respective wild-type (WT) littermates (n = 6 or 7/group, male) were fed a Se-adequate Torula yeast-sucrose diet and killed at 6 months of age to collect liver samples. In Exp. 1, fasted SOD1−/− mice displayed pyruvate intolerance and a 61% decrease (P < 0.05) in liver glycogen compared with the WT littermates. The former had lower (P < 0.05) activities of phosphoenolpyruvate carbooxykinase, total protein phosphatase, and protein phosphatase 2A, but a higher (P < 0.05) activity of glucokinase in the liver than those of the latter. In contrast, hepatic concentrations of total cholesterol, triglyceride, and non-esterified fatty acids were increased by 11 to 100% (P < 0.05) in the SOD1−/− mice. Meanwhile, these mice had elevated (P < 0.05) hepatic protein levels of sterol regulatory element binding proteins-1 and 2, p53 MAPK, total and phosphorylated AMP-activated protein kinase α1 protein, protein tyrosine phosphatase-1B, and protein phosphatase-2B. In Exp. 2, GPX1−/− and their WT littermates were compared, but showed no difference in any of the measures. In conclusion, knockout of SOD1, but not GPX1, led to a decreased liver glycogen storage synchronized with pyruvate intolerance and elevated hepatic lipid profiles in the adult mice. This striking comparison was possibly due to unique impacts of these two knockouts on intracellular tone of H2O2 and key regulators of liver gluconeogenesis, glycolysis, and lipogenesis.
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影响因子：
7.7
作者：
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通讯作者：
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DOI：
10.1016/s1098-3597(05)80069-9
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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作者：
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DOI：
10.1073/pnas.96.22.12737
发表时间：
1999-10-26
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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