PDPOB Exerts Multiaspect Anti-Ischemic Effects Associated with the Regulation of PI3K/AKT and MAPK Signaling Pathways
文献类型：期刊论文
| 作者 | Zhao, Qinyuan1,2; Shao, Xingcheng2,3; Ding, Xun1,2; Lin, Sijin1,2; Zhang, Dong4; Qin, Junjun2,3; Wang, Wei1; Yu, Weichen1,2; Zhang, Rujun3; Tao, Lingxue1 |
| 刊名 | ACS CHEMICAL NEUROSCIENCE
 |
| 出版日期 | 2021-10-21 |
| 卷号 | 12期号:23页码:4416-4427 |
| 关键词 | ischemic stroke n-pentyl 4-(3,4-dihydroxyphenyl)-4-oxobutanoate neuroprotection neuroinflammation MCAO |
| ISSN号 | 1948-7193 |
| DOI | 10.1021/acschemneuro.1c00459 |
| 通讯作者 | Tao, Lingxue(lingxuetao@simm.ac.cn) ; Zhao, Weimin(wmzhao@simm.ac.cn) ; Zhang, Haiyan(hzhang@simm.ac.cn) |
| 英文摘要 | The discovery of new therapeutic agents for ischemic stroke remains an urgent need. Here, we identified a novel phenyl carboxylic acid derivative, n-pentyl 4-(3,4-dihydroxyphenyl)-4-oxobutanoate (PDPOB), with anti-ischemic activities. The in vitro anti-ischemic neuroprotective and anti-inflammatory capacities of PDPOB were investigated using neuronal cells suffering from oxygen-glucose deprivation/reperfusion (OGD/R) and microglial cells stimulated by lipopolysaccharide (LPS). PDPOB attenuated the OGD/R-evoked cellular damage of SH-SYSY cells and primary cortical neurons in a concentration-dependent manner. Likewise, PDPOB displayed protective roles against OGD/R-evoked multiaspect neuronal deterioration in SH-SYSY cells, as evidenced by alleviated mitochondrial dysfunction, oxidative stress, and apoptosis. A further study unveiled the accelerated phosphorylation of protein kinase B (AKT) by PDPOB treatment, while blockade of phosphoinositide 3-kinase (PI3K)/AKT signaling substantially diminished the neuroprotective capacities of PDPOB. Additionally, the PDPOB pretreatment dampened the LPS-evoked neuroinflammation in BV2 cells, characterized by the suppressed secretion of nitric oxide (NO) and proinflammatory cytokines, as well as normalized expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Western blotting further revealed that PDPOB abated the overabundant phosphorylation of the extracellular signal-regulated kinase (ERIC), c-Jun-N-terminal kinase (JNK), and p38 in LPS-exposed BV2 cells. The intravenous application of PDPOB (30 mg/kg, single dose) attenuated ipsilateral cerebral infarction in middle cerebral artery occlusion (MCAO) rats, accompanied by recovered neurological behaviors. Collectively, the above observations provided substantial evidence for the favorable properties and mechanistic explanations of PDPOB in the regulation of ischemia-associated neuronal injury and microglial inflammation, which may furnish ideas for the discovery of new therapeutic strategies against cerebral ischemia. |
| WOS关键词 | NITRIC-OXIDE SYNTHASE ; STROKE ; CASPASE-3 ; LIPOPOLYSACCHARIDE ; ACTIVATION ; APOPTOSIS ; ISCHEMIA ; SURVIVAL ; ROLES ; BRAIN |
| 资助项目 | National Natural Science Foundation of China[81872859] ; National Natural Science Foundation of China[21877119] ; National ST Major Project[2018ZX09711002-002-014] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000730805800006 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300821]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Tao, Lingxue; Zhao, Weimin; Zhang, Haiyan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Nat Prod Chem, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Qinyuan,Shao, Xingcheng,Ding, Xun,et al. PDPOB Exerts Multiaspect Anti-Ischemic Effects Associated with the Regulation of PI3K/AKT and MAPK Signaling Pathways[J]. ACS CHEMICAL NEUROSCIENCE,2021,12(23):4416-4427. |
| APA | Zhao, Qinyuan.,Shao, Xingcheng.,Ding, Xun.,Lin, Sijin.,Zhang, Dong.,...&Zhang, Haiyan.(2021).PDPOB Exerts Multiaspect Anti-Ischemic Effects Associated with the Regulation of PI3K/AKT and MAPK Signaling Pathways.ACS CHEMICAL NEUROSCIENCE,12(23),4416-4427. |
| MLA | Zhao, Qinyuan,et al."PDPOB Exerts Multiaspect Anti-Ischemic Effects Associated with the Regulation of PI3K/AKT and MAPK Signaling Pathways".ACS CHEMICAL NEUROSCIENCE 12.23(2021):4416-4427. |
入库方式： OAI收割
来源：上海药物研究所
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