SOD3 decreases ischemic injury derived apoptosis through phosphorylation of Erk1/2, Akt, and FoxO3a.
SOD3 decreases ischemic injury derived apoptosis through phosphorylation of Erk1/2, Akt, and FoxO3a.
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DOI：
10.1371/journal.pone.0024456
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Laukkanen MO
中科院分区：
文献类型：
--
作者：
Laatikainen LE;Incoronato M;Castellone MD;Laurila JP;Santoro M;Laukkanen MO
细胞外超氧化物歧化酶（SOD3）将超氧化物阴离子歧化成过氧化氢，已被证明可以减少组织损伤中自由基应激引起的细胞凋亡。由于超氧阴离子和过氧化氢都对信号转导通路有显著影响，并可能解释不同病理条件下的许多凋亡和存活相关现象，因此我们明确了SOD3对大鼠后肢损伤模型中Akt和Erk1/2细胞存活通路的影响。根据我们的数据，与对照组相比，用病毒传递的sod3处理后肢缺血大鼠的损伤更轻，细胞凋亡更少，这可能是由于促增殖和抗凋亡的Erk1/2和Akt通路并行激活。在sod3处理的组织和细胞系中，这两种信号通路的共同下游因子，凋亡相关叉头盒蛋白O3a （FoxO3a）被磷酸化并转运到细胞质中。此外，我们发现elk-1、ets-1和microRNA 21 （miR-21）的mRNA产量增加，而sod3过表达组织中bim mRNA的合成减少。我们进一步发现，与受伤对照动物相比，sod3的过表达通过下调nox2和inos来调节氧化还原相关基因的表达。该研究表明，SOD3衍生的组织损伤恢复效应的复杂性并不局限于减少超氧阴离子引起的细胞应激，而是强调了SOD3相关信号转导对组织功能的影响，并提示SOD3在不同病理条件下对细胞应激效应的减弱具有重要作用。
Extracellular superoxide dismutase (SOD3), which dismutates superoxide anion to hydrogen peroxide, has been shown to reduce the free radical stress derived apoptosis in tissue injuries. Since both superoxide anion and hydrogen peroxide have a marked impact on signal transduction pathways and could potentially explain a number of apoptosis and survival -related phenomena in different pathological conditions, we clarified the impact of SOD3 on Akt and Erk1/2 cell survival pathways in rat hind limb injury model. Based on our data, the hind limb ischemic rats treated with virally delivered sod3 have milder injury and less apoptosis than control animals that could be due to parallel activation of pro-proliferative and anti-apoptotic Erk1/2 and Akt pathways. The common downstream factor of both signaling pathways, the apoptosis related forkhead box protein O3a (FoxO3a), was phosphorylated and translocated to the cytoplasm in sod3 treated tissues and cell line. Additionally, we obtained increased mRNA production of elk-1, ets-1, and microRNA 21 (miR-21), whereas synthesis of bim mRNA was decreased in sod3 overexpressing tissues. We further showed that overexpression of sod3 modulated redox related gene expression by downregulating nox2 and inos when compared to injured control animals. The study shows the complexity of SOD3-derived effects on tissue injury recovery that are not limited to the reduction of superoxide anion caused cellular stress but highlights the impact of SOD3 related signal transduction on tissue functions and suggests an important role for SOD3 in attenuating cell stress effects in different pathological conditions.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
5.2
作者：
Lei, Hong;Quelle, Frederick W.
通讯作者：
Quelle, Frederick W.
影响因子：
3.7
作者：
Oshikawa J;Urao N;Kim HW;Kaplan N;Razvi M;McKinney R;Poole LB;Fukai T;Ushio-Fukai M
通讯作者：
Ushio-Fukai M
影响因子：
37.8
作者：
Laukkanen, MO;Kivelä, A;Yla-Herttuala, S
通讯作者：
Yla-Herttuala, S
影响因子：
4
作者：
Huang, Haojie;Tindall, Donald J.
通讯作者：
Tindall, Donald J.