Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3.
Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3.
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白血病抑制因子通过上调超氧化物歧化酶3来保护神经元免受缺血性损害。
DOI：
10.1007/s12035-015-9587-2
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发表时间：
2017-01
影响因子：
5.1
通讯作者：
Pennypacker, Keith R.
中科院分区：
文献类型：
--
作者：
Davis, Stephanie M.;Collier, Lisa A.;Leonardo, Christopher C.;Seifert, Hilary A.;Ajmo, Craig T., Jr.;Pennypacker, Keith R.
白血病抑制因子（LIF）已被证明可以通过上调内源性抗氧化剂来保护少突胶质细胞免受缺血。本研究的目的是确定LIF是否通过上调超氧化物歧化酶3（SOD 3）在中风期间保护神经元。在大脑中动脉闭塞或假手术后6、24和48 h，对动物施用磷酸盐缓冲盐水（PBS）或125 μg/kg LIF。从胚胎第18天的大鼠幼仔中分离神经元，并在培养7至15天之间使用。用LIF和/或10 μM Akt抑制剂IV处理细胞，PBS和0.1%DMSO作为溶媒对照。用乱序或SOD 3小干扰RNA（siRNA）转染的神经元在PBS或LIF处理后经受24小时缺血。与PBS相比，LIF显著增加同侧脑组织中超氧化物歧化酶活性和SOD 3表达。24小时缺血后，LIF减少细胞死亡和增加SOD 3信使RNA（mRNA）在体外相比，PBS。加入Akt抑制剂IV和LIF抵消了细胞死亡的减少。在LIF处理之前使用siRNA部分沉默SOD 3的表达抵消了单独的LIF PBS处理的保护作用。这些结果表明LIF通过上调SOD 3在体内和体外保护神经元。
Leukemia inhibitory factor (LIF) has been shown to protect oligodendrocytes from ischemia by upregulating endogenous antioxidants. The goal of this study was to determine whether LIF protects neurons during stroke by upregulating superoxide dismutase 3 (SOD3). Animals were administered phosphate-buffered saline (PBS) or 125 μg/kg LIF at 6, 24, and 48 h after middle cerebral artery occlusion or sham surgery. Neurons were isolated from rat pups on embryonic day 18 and used between 7 and 15 days in culture. Cells were treated with LIF and/or 10 μM Akt inhibitor IV with PBS and 0.1 % DMSO acting as vehicle controls. Neurons transfected with scrambled or SOD3 small interfering RNA (siRNA) were subjected to 24-h ischemia after PBS or LIF treatment. LIF significantly increased superoxide dismutase activity and SOD3 expression in ipsilateral brain tissue compared to PBS. Following 24-h ischemia, LIF reduced cell death and increased SOD3 messenger RNA (mRNA) in vitro compared to PBS. Adding Akt inhibitor IV with LIF counteracted the decrease in cell death. Partially silencing the expression of SOD3 using siRNA prior to LIF treatment counteracted the protective effect of LIF-alone PBS treatment. These results indicate that LIF protects neurons in vivo and in vitro via upregulation of SOD3.
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影响因子：
2.1
作者：
Ajmo, Craig T., Jr.;Vernon, Dionne O. L.;Cuevas, Javier
通讯作者：
Cuevas, Javier
影响因子：
4.8
作者：
Blanchard, F;Duplomb, L;Baumann, H
通讯作者：
Baumann, H
DOI：
10.1073/pnas.92.16.7162
发表时间：
1995-08-01
影响因子：
11.1
作者：
BONFOCO, E;KRAINC, D;LIPTON, SA
通讯作者：
LIPTON, SA
影响因子：
3.5
作者：
Alonzi, T;Middleton, G;Davies, AM
通讯作者：
Davies, AM
影响因子：
9.3
作者：
Chen X;Guan T;Li C;Shang H;Cui L;Li XM;Kong J
通讯作者：
Kong J