ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells
博士 === 國立中興大學 === 生命科學系所 === 104 === Release of calcium (Ca++) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca++ release dantrolene and inhibitor of mitochondrial Ca++ uptake Ru-360, we demonstrated here tha...
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ndltd-TW-104NCHU51050622019-05-15T23:00:43Z http://ndltd.ncl.edu.tw/handle/m869js ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells 內質網依賴之鈣離子所介導之細胞質ROS為沒食子酸處理的人類口腔癌細胞中粒線體凋亡訊號與ATM-JNK訊息路徑的誘導者 Yao-Cheng Lu 呂曜呈 博士 國立中興大學 生命科學系所 104 Release of calcium (Ca++) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca++ release dantrolene and inhibitor of mitochondrial Ca++ uptake Ru-360, we demonstrated here that Ca++ release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose-regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca++ increase and apoptosis, but did not attenuate the increase in cytosolic Ca++ level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM)-mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by the treatment with N-acetylcysteine, an ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. When taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca++-mediated ROS production. Hong-Lin Su Shih-Shun Chen 蘇鴻麟 陳世順 2016 學位論文 ; thesis 45 zh-TW |
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博士 === 國立中興大學 === 生命科學系所 === 104 === Release of calcium (Ca++) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca++ release dantrolene and inhibitor of mitochondrial Ca++ uptake Ru-360, we demonstrated here that Ca++ release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose-regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca++ increase and apoptosis, but did not attenuate the increase in cytosolic Ca++ level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM)-mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by the treatment with N-acetylcysteine, an ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. When taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca++-mediated ROS production.
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author2 |
Hong-Lin Su |
author_facet |
Hong-Lin Su Yao-Cheng Lu 呂曜呈 |
author |
Yao-Cheng Lu 呂曜呈 |
spellingShingle |
Yao-Cheng Lu 呂曜呈 ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells |
author_sort |
Yao-Cheng Lu |
title |
ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells |
title_short |
ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells |
title_full |
ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells |
title_fullStr |
ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells |
title_full_unstemmed |
ER-Dependent Ca++-Mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells |
title_sort |
er-dependent ca++-mediated cytosolic ros as an effector for induction of mitochondrial apoptotic and atm-jnk signal pathways in gallic acid-treated human oral cancer cells |
publishDate |
2016 |
url |
http://ndltd.ncl.edu.tw/handle/m869js |
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