Catalpol Inhibits Ischemia-Induced Premyelinating Oligodendrocyte Damage through Regulation of Intercellular Calcium Homeostasis via Na⁺/Ca(2+) Exchanger 3.
Catalpol Inhibits Ischemia-Induced Premyelinating Oligodendrocyte Damage through Regulation of Intercellular Calcium Homeostasis via Na⁺/Ca(2+) Exchanger 3.
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梓醇通过 Naα/Ca2 交换器 3 调节细胞间钙稳态，抑制缺血诱导的髓鞘形成前少突胶质细胞损伤
DOI：
10.3390/ijms19071925
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发表时间：
2018-06-30
影响因子：
5.6
通讯作者：
Li H
中科院分区：
文献类型：
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作者：
Cai Q;Ma T;Tian Y;Li C;Li H
早髓鞘少突胶质细胞对缺氧缺血反应的易感性增加可能导致围产期脑白质损伤和随后的神经行为功能障碍。细胞内钙超载被认为是易感细胞发生缺血性损伤的重要机制。我们先前报道了从地黄中提取的环烯醚萜糖苷梓醇在体外缺血模型中抑制细胞内钙超载的作用。然而，确切的潜在机制仍然难以捉摸。在本研究中，我们旨在研究梓醇对PreOLS的保护作用，并探讨参与调节细胞内钙稳态的潜在机制。出生后第2天(P2)SD大鼠结扎双侧颈总动脉，然后暴露于8%氧气10min，作为新生大鼠缺氧缺血模型。我们发现，梓醇能显著改善行为功能，防止缺氧缺血后Preol丢失和髓鞘形成障碍。我们的体外研究也证实了梓醇对氧-葡萄糖剥夺(OGD)诱导的细胞死亡和前OOL成熟受阻的直接作用。此外，我们还发现梓醇能显著抑制细胞内钙超载，促进Na+/Ca2+交换器3(NCX3)的表达。最后，我们发现梓醇显著降低线粒体损伤和随后的细胞外信号调节激酶1/2(ERK1/2)和多聚ADP核糖聚合酶-1(PARP-1)的激活。NCX3受体拮抗剂2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea(KB-R7943)可显著逆转梓醇对缺氧性脑损伤前脂肪细胞的保护作用。总体而言，我们的数据表明，梓醇通过上调NCX3活性来调节细胞间钙稳态，从而保护PreOLS免受缺血损伤。
The heightened vulnerability of premyelinating oligodendrocytes (PreOLs) in response to hypoxia–ischemia may contribute to perinatal white matter injury and subsequent neurobehavioral dysfunction. Intracellular Ca2+ overload is considered a crucial mechanism predisposing PreOLs to ischemic injury. We previously reported that catalpol, an iridoid glycoside extracted from Rehmannia root, inhibits intracellular Ca2+ overload of PreOLs in an in vitro ischemia model. However, the exact underlying mechanisms remain elusive. In the present study, we aimed to investigate the protective effects of catalpol on PreOLs and to explore the underlying mechanisms involved in the modulation of intracellular Ca2+ homeostasis. Postnatal day 2 (P2) Sprague-Dawley (SD) rats subjected to bilateral common carotid artery ligation followed by exposure to 8% oxygen for 10 min were used as a rat model of neonatal hypoxia–ischemia. We found that catalpol significantly improved behavioral functions and prevented PreOL loss and myelination deficit after hypoxia–ischemia. Our in vitro studies also confirmed the direct effects of catalpol on oxygen-glucose deprivation (OGD)-induced cell death and arrested maturation of PreOLs. Moreover, we demonstrated that catalpol significantly inhibited intracellular Ca2+ overload and promoted the expression of Na+/Ca2+ exchanger 3 (NCX3). Finally, we found that catalpol significantly reduced mitochondrial damage and subsequent extracellular signal-regulated kinase 1/2 (ERK1/2) and poly-ADP-ribose polymerase-1 (PARP-1) activation. Treatment with NCX3-preferring inhibitor 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943) significantly reversed the protective effects of catalpol on PreOLs under OGD. Overall, our data suggest that catalpol protects PreOLs from ischemic injury through regulation of intercellular Ca2+ homeostasis via upregulation of NCX3 activity.
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DOI：
10.1196/annals.1387.050
发表时间：
2007-01-01
期刊：
SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE
影响因子：
--
作者：
Annunziato, L.;Pignataro, G.;Di Renzo, G. E.
通讯作者：
Di Renzo, G. E.
影响因子：
6.2
作者：
Domercq, Maria;Perez-Samartin, Alberto;Matute, Carlos
通讯作者：
Matute, Carlos
梓醇通过 Akt 信号通路促进慢性脑灌注不足大鼠少突胶质细胞存活和少突胶质细胞祖细胞分化
影响因子：
2.9
作者：
Cai, Qiyan;Yao, Zhongxiang;Li, Hongli
通讯作者：
Li, Hongli
影响因子：
3.6
作者：
Dinicola, Simona;Mariggio, Maria Addolorata;Bizzarri, Mariano
通讯作者：
Bizzarri, Mariano
影响因子：
6.2
作者：
Casamassa, Antonella;La Rocca, Claudia;Boscia, Francesca
通讯作者：
Boscia, Francesca