Brain-derived neurotrophic factor increases expression of MnSOD in human circulating angiogenic cells.
Brain-derived neurotrophic factor increases expression of MnSOD in human circulating angiogenic cells.
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DOI：
10.1016/j.mvr.2012.01.001
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发表时间：
2012-05
影响因子：
3.1
通讯作者：
Katusic ZS
中科院分区：
文献类型：
--
作者：
He T;Katusic ZS
现有证据表明，脑源性神经营养因子（BDNF）促进内皮细胞的存活和增殖，刺激造血祖细胞的动员，并诱导缺血组织中的血管生成。然而，BDNF的血管保护功能的机制还知之甚少。我们假设BDNF增加循环血管生成细胞的抗氧化能力。从30名健康男性志愿者（48 ± 2岁）的外周血中分离人单核细胞，并在内皮生长培养基-2中培养4-5天。附着的细胞（所谓的早期内皮祖细胞[早期EPCs]，或循环血管生成细胞）表达BDNF受体、原肌球蛋白相关激酶B和p75神经营养因子受体。用重组人BDNF处理早期EPCs 24 h显著增加锰超氧化物歧化酶（MnSOD）的表达，但对其他抗氧化酶包括铜锌SOD（CuZnSOD）、过氧化氢酶和谷胱甘肽过氧化物酶-1的表达没有影响。BDNF刺激IκB激酶（IKK）α/β和应激活化蛋白激酶/c-Jun N-末端激酶（SAPK/JNK）的磷酸化;但它不激活p38、Erk或AKT。用核因子κB抑制剂PDTC或JNK抑制剂SP 600125处理，减弱BDNF增强的MnSOD蛋白表达。BDNF处理抑制由超氧阴离子发生器LY 83583诱导的细胞凋亡和血清饥饿诱导的细胞脱离。这些结果表明，BDNF保护EPCs通过增加MnSOD的表达，从而提高其抗氧化能力。
Existing evidence suggests that brain-derived neurotrophic factor (BDNF) promotes survival and proliferation of endothelial cells, stimulates mobilization of hematopoietic progenitors, and induces angiogenesis in ischemic tissues. However, the mechanisms underlying vascular protective function of BDNF are poorly understood. We hypothesized that BDNF increases antioxidant capacity of circulating angiogenic cells. Human mononuclear cells were isolated from peripheral blood of 30 healthy male volunteers (48 ± 2 years old), and cultured in endothelial growth medium-2 for 4–5 days. The attached cells (so called early endothelial progenitor cells [early EPCs], or circulating angiogenic cells) expressed BDNF receptors, tropomyosin-related kinase B and p75 neurotrophin receptor. Treatment of early EPCs with recombinant human BDNF for 24 h significantly increased manganese superoxide dismutase (MnSOD) expression, but had no effect on expression of other antioxidant enzymes including copper zinc SOD (CuZnSOD), catalase, and glutathione peroxidase-1. BDNF stimulated phosphorylation of IκB kinase (IKK)α/β and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK); however it did not activate p38, Erk, or AKT. Treatment with nuclear factor κB inhibitor, PDTC, or JNK inhibitor, SP600125, attenuated BDNF-augmented MnSOD protein expression. BDNF treatment inhibited apoptosis induced by a superoxide anion generator LY83583, and serum starvation-induced cell detachment. These findings suggest that BDNF protect EPCs by increasing expression of MnSOD thereby enhancing their antioxidant capacity.
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影响因子：
6
作者：
Liu, Xialin;Li, Yongjun;Goldschmidt-Clermont, Pascal J.
通讯作者：
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影响因子：
20.1
作者：
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影响因子：
3.1
作者：
He, Tongrong;Joyner, Michael J.;Katusic, Zvonimir S.
通讯作者：
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影响因子：
11.2
作者：
Arumugam, Thiruma V.;Phillips, Terry M.;Cheng, Aiwu;Morrell, Christopher H.;Mattson, Mark P.;Wan, Ruiqian
通讯作者：
Wan, Ruiqian
影响因子：
15.9
作者：
Kermani, P;Rafii, D;Hempstead, BL
通讯作者：
Hempstead, BL