Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis.
Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis.
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DOI：
10.1016/j.fob.2014.05.003
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发表时间：
2014
期刊：
影响因子：
2.6
通讯作者：
Ishigami, Akihito
中科院分区：
文献类型：
--
作者：
Kondo, Yoshitaka;Masutomi, Hirofumi;Noda, Yoshihiro;Ozawa, Yusuke;Takahashi, Keita;Handa, Setsuko;Maruyama, Naoki;Shimizu, Takahiko;Ishigami, Akihito
我们产生了SMP 30/SOD 1双敲除（DKO）小鼠用于氧化应激研究。SMP 30/SOD 1-DKO小鼠表现出低水平的抗坏血酸和过早死亡。SMP 30/SOD 1-DKO小鼠表现出高水平的氧化应激和肝损伤。由于载脂蛋白B水平降低，SMP 30/SOD 1-DKO小鼠表现出肝脂肪变性。超氧化物歧化酶1（SOD 1）是一种抗氧化酶，可将超氧阴离子自由基转化为过氧化氢和分子氧。衰老标记蛋白-30（SMP 30）是一种脂肪酸内酯酶，由于其参与抗坏血酸（AA）的生物合成而在哺乳动物中作为抗氧化剂蛋白发挥作用。SMP 30还通过激活钙调素依赖性Ca 2+泵参与Ca 2+流出。为了揭示氧化应激在非酒精性脂肪性肝病发病机制中脂质代谢缺陷中的作用，我们产生了SMP 30/SOD 1-DKO小鼠，并研究了其存活曲线，血浆和肝脏脂质谱，肝脏氧化应激量以及脂质代谢相关基因表达的肝脏蛋白水平。虽然SMP 30/SOD 1-DKO幼仔在14日龄时没有生长迟缓，但它们确实具有低血浆和肝脏AA水平。此后，分别有39%和53%的雄性和雌性幼仔在15-24天和89天龄时死亡。与野生型、SMP 30-KO和SOD 1-KO小鼠相比，14天时，SMP 30/SOD 1-DKO小鼠表现出：（1）血浆甘油三酯和天冬氨酸转氨酶水平升高，（2）肝脏甘油三酯和总胆固醇严重蓄积，（3）肝脏超氧阴离子自由基和硫代巴比妥酸反应物水平升高，（4）肝组织中甘油三酯和总胆固醇水平升高。（4）肝脏中载脂蛋白B（ApoB）的mRNA和蛋白水平降低- ApoB是VLDL分泌的重要组分。这些结果表明，高水平的氧化应激，由于伴随的缺陷的SMP 30和/或AA，和SOD 1导致异常的血浆脂质代谢，肝脂质积累和过早死亡，导致VLDL分泌受损。
We generated SMP30/SOD1-double knockout (DKO) mice for oxidative stress research. SMP30/SOD1-DKO mice showed low levels of ascorbic acid and premature death. SMP30/SOD1-DKO mice exhibited high levels of oxidative stress and liver injury. SMP30/SOD1-DKO mice manifest hepatic steatosis due to decreased levels of Apolipoprotein B. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30) is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA) biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO) mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1) higher plasma levels of triglyceride and aspartate aminotransferase; (2) severe accumulation of hepatic triglyceride and total cholesterol; (3) higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4) decreased mRNA and protein levels of Apolipoprotein B (ApoB) in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion.
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影响因子：
1.6
作者：
Amano, Akiko;Sato, Yasunori;Ishigami, Akihito
通讯作者：
Ishigami, Akihito
DOI：
10.1006/bbrc.1998.9327
发表时间：
1998-09-18
影响因子：
3.1
作者：
Fujita, T;Inoue, H;Maruyama, N
通讯作者：
Maruyama, N
影响因子：
4.8
作者：
Andreo, Ursula;Elkind, Josh;Fisher, Edward A.
通讯作者：
Fisher, Edward A.
影响因子：
4.3
作者：
Basaranoglu, Metin;Basaranoglu, Gokcen;Senturk, Hakan
通讯作者：
Senturk, Hakan
影响因子：
5.5
作者：
Laing, Suzette;Wang, Guohui;Zhang, Kezhong
通讯作者：
Zhang, Kezhong