L-Cysteine-Derived H2S Promotes Microglia M2 Polarization via Activation of the AMPK Pathway in Hypoxia-Ischemic Neonatal Mice
L-Cysteine-Derived H2S Promotes Microglia M2 Polarization via Activation of the AMPK Pathway in Hypoxia-Ischemic Neonatal Mice
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L-半胱氨酸衍生的 H2S 通过激活缺氧缺血新生小鼠的 AMPK 途径促进小胶质细胞 M2 极化
DOI：
10.3389/fnmol.2019.00058
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Wang Zhen
中科院分区：
文献类型：
--
作者：
Zhou Xin;Chu Xili;Xin Danqing;Li Tong;Bai Xuemei;Qiu Jie;Yuan Hongtao;Liu Dexiang;Wang Dachuan;Wang Zhen
我们以前曾报道，L-半胱氨酸衍生的硫化氢（H2S）表现出显着的神经保护作用，对缺氧缺血（HI）的伤害在新生动物。在这里，我们评估了L-半胱氨酸发挥这种保护作用的一些机制。具体而言，我们研究了L-半胱氨酸刺激M2表型的小胶质细胞极化及其对新生小鼠中响应HI的补体表达的调节的能力。L-半胱氨酸治疗抑制了炎症细胞因子的产生，同时显著上调了受损皮质中抗炎细胞因子的水平。这种L-半胱氨酸给药促进小胶质细胞从炎性M1转化为抗炎M2表型，这种作用与抑制p38和/或JNK促炎途径、核因子-κB活化和HI衍生的C1 q、C3 a和C3 a补体受体蛋白水平降低相关。值得注意的是，H2S产生的阻断明显阻止了L-半胱氨酸介导的M2极化和补体表达。L-半胱氨酸也抑制神经元凋亡诱导的条件培养基从激活的M1小胶质细胞在体外。我们还表明，L-半胱氨酸促进AMP激活蛋白激酶（AMPK）的激活和AMPK抑制剂废除这些抗凋亡和抗炎作用的L-半胱氨酸。总之，我们的研究结果表明，L-半胱氨酸衍生的H2S衰减HI后的神经元凋亡，并表明这些影响，部分是由于增强小胶质细胞M2极化和通过AMPK激活调节补体表达。
We have reported previously that L-cysteine-derived hydrogen sulfide (H2S) demonstrates a remarkable neuroprotective effect against hypoxia-ischemic (HI) insult in neonatal animals. Here, we assessed some of the mechanisms of this protection as exerted by L-cysteine. Specifically, we examined the capacity for L-cysteine to stimulate microglial polarization of the M2 phenotype and its modulation of complement expression in response to HI in neonatal mice. L-cysteine treatment suppressed the production of inflammatory cytokines, while dramatically up-regulating levels of anti-inflammatory cytokines in the damaged cortex. This L-cysteine administration promoted the conversion of microglia from an inflammatory M1 to an anti-inflammatory M2 phenotype, an effect which was associated with inhibiting the p38 and/or JNK pro-inflammatory pathways, nuclear factor-κB activation and a decrease in HI-derived levels of the C1q, C3a and C3a complement receptor proteins. Notably, blockade of H2S-production clearly prevented L-cysteine-mediated M2 polarization and complement expression. L-cysteine also inhibited neuronal apoptosis as induced by conditioned media from activated M1 microglia in vitro. We also show that L-cysteine promoted AMP-activated protein kinase (AMPK) activation and the AMPK inhibitor abolished these anti-apoptotic and anti-inflammatory effects of L-cysteine. Taken together, our findings demonstrate that L-cysteine-derived H2S attenuated neuronal apoptosis after HI and suggest that these effects, in part, result from enhancing microglia M2 polarization and modulating complement expression via AMPK activation.
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影响因子：
--
作者：
Shefa U;Kim MS;Jeong NY;Jung J
通讯作者：
Jung J
DOI：
10.1007/978-3-642-54596-2_1581
发表时间：
2014
期刊：
--
影响因子：
--
作者：
C. Padro;V. Sanders
通讯作者：
C. Padro;V. Sanders
影响因子：
8.3
作者：
Nijboer, Cora H.;Heijnen, Cobi J.;Kavelaars, Annemieke
通讯作者：
Kavelaars, Annemieke
DOI：
--
发表时间：
2007
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
N. Perkins
通讯作者：
N. Perkins
影响因子：
7.4
作者：
Oh, Gi-Su;Pae, Hyun-Ock;Chung, Hun-Taeg
通讯作者：
Chung, Hun-Taeg