DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways
DiDang Tang (DDT), a Chinese traditional medicine formula, contains 4 Chinese traditional medicine substances, has been widely used to treat intracerebral hemorrhage (ICH) patients. However, the molecular mechanisms of DDT for protecting neurons from oxygen and glucose deprivation (OGD)-induced endo...
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01423/full |
| _version_ | 1811280537673793536 |
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| author | Qingxia Huang Qingxia Huang Tianye Lan Jing Lu Jing Lu He Zhang He Zhang Dongmei Zhang Tingting Lou Tingting Lou Peng Xu Jixiang Ren Daqing Zhao Daqing Zhao Liwei Sun Xiangyan Li Xiangyan Li Jian Wang |
| author_facet | Qingxia Huang Qingxia Huang Tianye Lan Jing Lu Jing Lu He Zhang He Zhang Dongmei Zhang Tingting Lou Tingting Lou Peng Xu Jixiang Ren Daqing Zhao Daqing Zhao Liwei Sun Xiangyan Li Xiangyan Li Jian Wang |
| author_sort | Qingxia Huang |
| collection | DOAJ |
| description | DiDang Tang (DDT), a Chinese traditional medicine formula, contains 4 Chinese traditional medicine substances, has been widely used to treat intracerebral hemorrhage (ICH) patients. However, the molecular mechanisms of DDT for protecting neurons from oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum (ER) stress and apoptosis after ICH still remains elusive. In this study, high-performance liquid chromatography fingerprint analysis was performed to learn the features of the chemical compositions of DDT. OGD-induced ER stress, Ca2+ overload, and mitochondrial apoptosis were investigated in nerve growth factor -induced PC12, primary neuronal cells, and ICH rats to evaluate the protective effect of DDT. We found that DDT treatment protected neurons against OGD-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. DDT decreased OGD-induced Ca2+ overload and ER stress through the blockade of the glucose-regulated protein 78 (GRP78)- inositol-requiring protein 1α (IRE1)/ protein kinase RNA-like ER kinase (PERK) pathways and also inhibited apoptosis by decreasing mitochondrial damage. Moreover, we observed similar findings when we studied DDT for inhibition of ER stress in a rat model of ICH. In addition, our experiments further confirmed the neuroprotective potential of DDT against tunicamycin (TM)-induced neural damage. Our in vitro and in vivo results indicated that the neuroprotective effect of DDT against ER stress damage and apoptosis occurred mainly by blocking the GPR78-IRE1/PERK pathways. Taken together, it provides reliable experimental evidence and explains the molecular mechanism of DDT for the treatment of patients with ICH. |
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| language | English |
| last_indexed | 2024-04-13T01:16:36Z |
| publishDate | 2018-12-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-6af68f9448244280b9a4739e0582ef1b2022-12-22T03:08:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-12-01910.3389/fphar.2018.01423418283DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK PathwaysQingxia Huang0Qingxia Huang1Tianye Lan2Jing Lu3Jing Lu4He Zhang5He Zhang6Dongmei Zhang7Tingting Lou8Tingting Lou9Peng Xu10Jixiang Ren11Daqing Zhao12Daqing Zhao13Liwei Sun14Xiangyan Li15Xiangyan Li16Jian Wang17Research Center of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Provincial Key Laboratory of BioMacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Encephalopathy, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Provincial Key Laboratory of BioMacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Provincial Key Laboratory of BioMacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaScientific Research Office, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Provincial Key Laboratory of BioMacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Encephalopathy, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Encephalopathy, Changchun University of Chinese Medicine, Changchun, ChinaJilin Provincial Key Laboratory of BioMacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Provincial Key Laboratory of BioMacromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaJilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, ChinaDepartment of Encephalopathy, Changchun University of Chinese Medicine, Changchun, ChinaDiDang Tang (DDT), a Chinese traditional medicine formula, contains 4 Chinese traditional medicine substances, has been widely used to treat intracerebral hemorrhage (ICH) patients. However, the molecular mechanisms of DDT for protecting neurons from oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum (ER) stress and apoptosis after ICH still remains elusive. In this study, high-performance liquid chromatography fingerprint analysis was performed to learn the features of the chemical compositions of DDT. OGD-induced ER stress, Ca2+ overload, and mitochondrial apoptosis were investigated in nerve growth factor -induced PC12, primary neuronal cells, and ICH rats to evaluate the protective effect of DDT. We found that DDT treatment protected neurons against OGD-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. DDT decreased OGD-induced Ca2+ overload and ER stress through the blockade of the glucose-regulated protein 78 (GRP78)- inositol-requiring protein 1α (IRE1)/ protein kinase RNA-like ER kinase (PERK) pathways and also inhibited apoptosis by decreasing mitochondrial damage. Moreover, we observed similar findings when we studied DDT for inhibition of ER stress in a rat model of ICH. In addition, our experiments further confirmed the neuroprotective potential of DDT against tunicamycin (TM)-induced neural damage. Our in vitro and in vivo results indicated that the neuroprotective effect of DDT against ER stress damage and apoptosis occurred mainly by blocking the GPR78-IRE1/PERK pathways. Taken together, it provides reliable experimental evidence and explains the molecular mechanism of DDT for the treatment of patients with ICH.https://www.frontiersin.org/article/10.3389/fphar.2018.01423/fulloxygen and glucose deprivationendoplasmic reticulum stress (ER stress)DiDang Tangmitochondrial dysfunctionapoptosisGRP78-IRE1/PERK pathways |
| spellingShingle | Qingxia Huang Qingxia Huang Tianye Lan Jing Lu Jing Lu He Zhang He Zhang Dongmei Zhang Tingting Lou Tingting Lou Peng Xu Jixiang Ren Daqing Zhao Daqing Zhao Liwei Sun Xiangyan Li Xiangyan Li Jian Wang DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways Frontiers in Pharmacology oxygen and glucose deprivation endoplasmic reticulum stress (ER stress) DiDang Tang mitochondrial dysfunction apoptosis GRP78-IRE1/PERK pathways |
| title | DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways |
| title_full | DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways |
| title_fullStr | DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways |
| title_full_unstemmed | DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways |
| title_short | DiDang Tang Inhibits Endoplasmic Reticulum Stress-Mediated Apoptosis Induced by Oxygen Glucose Deprivation and Intracerebral Hemorrhage Through Blockade of the GRP78-IRE1/PERK Pathways |
| title_sort | didang tang inhibits endoplasmic reticulum stress mediated apoptosis induced by oxygen glucose deprivation and intracerebral hemorrhage through blockade of the grp78 ire1 perk pathways |
| topic | oxygen and glucose deprivation endoplasmic reticulum stress (ER stress) DiDang Tang mitochondrial dysfunction apoptosis GRP78-IRE1/PERK pathways |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01423/full |
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