Rapid, Nitric Oxide Synthesis-Dependent Activation of MMP-9 at Pericyte Somata During Capillary Ischemia in vivo.
Rapid, Nitric Oxide Synthesis-Dependent Activation of MMP-9 at Pericyte Somata During Capillary Ischemia in vivo.
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DOI：
10.3389/fphys.2020.619230
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发表时间：
2020
影响因子：
4
通讯作者：
Shih AY
中科院分区：
文献类型：
--
作者：
Underly RG;Shih AY
一氧化氮在正常的血管生理学中起着重要作用，但矛盾的是，它有助于疾病中的血管病理学。在脑缺血期间，异常的一氧化氮水平可通过诱导亚硝化/氧化应激和基质金属蛋白酶-9（MMP-9）的翻译后激活而引起细胞损伤。我们最近发现，脑周细胞胞体与脑缺血时沿毛细血管沿着的非常早期和局部MMP-9活化相关，导致局灶性血脑屏障破坏。在这里，我们测试了这种效应是否取决于一氧化氮的产生。在体内双光子成像被用来直接可视化MMP 9的活动，使用FITC-明胶探针和泄漏的静脉内染料在光血栓诱导的毛细血管缺血。结果表明，NOS抑制剂，L-NIL，在浓度影响iNOS和组成型NOS亚型，衰减毛细血管渗漏在周细胞胞体特异性的位置，并大大减少FITC-明胶裂解。我们还发现，L-NIL和茴香霉素（一种蛋白质合成抑制剂）的联合给药导致FITC-明胶裂解和血管渗漏几乎完全消除。这些结果表明，一氧化氮合酶和新的蛋白质的合成参与缺血时毛细血管周细胞胞体MMP-9的快速激活。
Nitric oxide serves essential roles in normal vascular physiology, but paradoxically contributes to vascular pathology in disease. During brain ischemia, aberrant nitric oxide levels can cause cellular injury through induction of nitrosative/oxidative stress and post-translational activation of matrix-metalloproteinase-9 (MMP-9). We recently demonstrated that brain pericyte somata were associated with very early and localized MMP-9 activation along capillaries during cerebral ischemia, leading to focal blood-brain barrier disruption. Here, we tested whether this effect was dependent upon nitric oxide production. In vivo two-photon imaging was used to directly visualize MMP9 activity using a FITC-gelatin probe and leakage of intravenous dye during photothrombotically induced capillary ischemia. Results showed that the NOS inhibitor, L-NIL, at concentrations affecting both iNOS and constitutive NOS isoforms, attenuated capillary leakage at pericyte soma-specific locations and substantially reduced FITC-gelatin cleavage. We also found that combined administration of L-NIL and anisomycin, an inhibitor of protein synthesis, led to near complete elimination of FITC-gelatin cleavage and vascular leakage. These results indicate that both nitric oxide synthase and new protein synthesis are involved in the rapid activation of MMP-9 at somata of capillary pericytes during ischemia.
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影响因子：
1.5
作者：
Cuttler, Anne S.;LeClair, Renee J.;Stohn, J. Patrizia;Wang, Qiaozeng;Sorenson, Christine M.;Liaw, Lucy;Lindner, Volkhard
通讯作者：
Lindner, Volkhard
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H
影响因子：
--
作者：
Bradley SA;Steinert JR
通讯作者：
Steinert JR
影响因子：
16.2
作者：
Hill, Robert A.;Tong, Lei;Yuan, Peng;Murikinati, Sasidhar;Gupta, Shobhana;Grutzendler, Jaime
通讯作者：
Grutzendler, Jaime
影响因子：
6.1
作者：
Planas, AM;Solé, S;Justicia, C
通讯作者：
Justicia, C