SOD1 overexpression in vivo blocks hyperglycemia-induced specific PKC isoforms: substrate activation and consequent lipid peroxidation in diabetic embryopathy.
SOD1 overexpression in vivo blocks hyperglycemia-induced specific PKC isoforms: substrate activation and consequent lipid peroxidation in diabetic embryopathy.
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DOI：
10.1016/j.ajog.2011.02.071
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发表时间：
2011-07
影响因子：
9.8
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Li X;Weng H;Reece EA;Yang P
氧化应激在糖尿病胚胎病中起致病作用。我们使用超氧化物歧化酶1 （SOD1）转基因小鼠测试了减轻氧化应激是否会阻断高血糖诱导的特异性PKC异构体激活及其下游级联反应。采用非糖尿病WT对照（NC）、糖尿病WT （DM）和糖尿病SOD1-Tg小鼠（DM-SOD1-Tg）第8.5天（E8.5）的胚胎，检测磷酸化（p-） PKCα/βII和p-PKCδ，以及两种PKC底物p- marcks和RACK1的水平，以及脂质过氧化标志物4-羟基壬烯醛（4-HNE）和丙二醛（MDA）的水平。与NC组和DM- sod1 - tg组相比，DM组p-PKCα/βII、p-PKCδ、p-MARCKS、4-HNE和MDA水平显著升高。NC组和DM-SOD1-Tg组具有相当水平的这些蛋白质和脂质过氧化标志物。RACK1水平在三组之间没有差异。通过SOD1过表达减轻氧化应激可阻断母体高血糖诱导的特定PKC亚型激活和下游级联反应。
Oxidative stress plays a causative role in diabetic embryopathy. We tested whether mitigating oxidative stress, using superoxide dismutase 1 (SOD1) transgenic mice, would block hyperglycemia-induced specific PKC isoform activation and its downstream cascade. Day 8.5 (E8.5) embryos from non-diabetic WT control (NC), diabetic mellitus WT (DM) and diabetic SOD1-Tg mice (DM-SOD1-Tg) were used for detection of phosphorylated (p-) PKCα/βII and p-PKCδ, and levels of two prominent PKC substrates, p-MARCKS and RACK1, and lipidperoxidation markers, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Levels of p-PKCα/βII, p-PKCδ, p-MARCKS, 4-HNE and MDA were significantly elevated in the DM group compared with those in the NC group and the DM-SOD1-Tg group. The NC and DM-SOD1-Tg groups had comparable levels of these protein and lipidperoxidation markers. RACK1 levels did not differ among the three groups. Mitigating oxidative stress by SOD1 overexpression blocks maternal hyperglycemia-induced activation of specific PKC isoforms and downstream cascades.
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影响因子：
9.8
作者：
Reece, EA;Wu, YK;Dhanasekaran, D
通讯作者：
Dhanasekaran, D
影响因子：
3.3
作者：
Gaereskog, Mattias;Cederberg, Jonas;Wentzel, Patti
通讯作者：
Wentzel, Patti
DOI：
10.1016/s0002-9378(96)80005-6
发表时间：
1996-10-01
影响因子：
9.8
作者：
Reece, EA;Wu, YK;Sloskey, G
通讯作者：
Sloskey, G
影响因子：
64.8
作者：
THELEN, M;ROSEN, A;ADEREM, A
通讯作者：
ADEREM, A
影响因子：
8
作者：
Chang, BY;Harte, RA;Cartwright, CA
通讯作者：
Cartwright, CA