Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation
Neurodegenerative disorders and brain damage are initiated by excessive production of reactive oxygen species (ROS), which leads to tissue injury, cellular death and inflammation. In cellular anti-oxidant systems, heme oxygenase-1 (HO-1) is an oxidative-sensor protein induced by ROS generation or ca...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2017-11-01
|
Series: | Frontiers in Molecular Neuroscience |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00387/full |
id |
doaj-24b6d9d974394af488b64ee1f5660a5c |
---|---|
record_format |
Article |
spelling |
doaj-24b6d9d974394af488b64ee1f5660a5c2020-11-24T20:53:44ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-11-011010.3389/fnmol.2017.00387300172Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated NeuroinflammationChih-Chung Lin0Chien-Chung Yang1Chien-Chung Yang2Li-Der Hsiao3Ssu-Yu Chen4Chuen-Mao Yang5Chuen-Mao Yang6Chuen-Mao Yang7Department of Anesthetics, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University, Tao-Yuan, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, TaiwanDepartment of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Tao-Yuan, TaiwanDepartment of Anesthetics, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University, Tao-Yuan, TaiwanDepartment of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Tao-Yuan, TaiwanDepartment of Anesthetics, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University, Tao-Yuan, TaiwanDepartment of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Tao-Yuan, TaiwanResearch Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, TaiwanNeurodegenerative disorders and brain damage are initiated by excessive production of reactive oxygen species (ROS), which leads to tissue injury, cellular death and inflammation. In cellular anti-oxidant systems, heme oxygenase-1 (HO-1) is an oxidative-sensor protein induced by ROS generation or carbon monoxide (CO) release. CO releasing molecules (CORMs), including CORM-3, exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanisms of CORM-3-induced HO-1 expression and protection against interleukin (IL)-1β-induced inflammatory responses have not been fully elucidated in rat brain astrocytes (RBA-1). To study the regulation of CORM-3-induced HO-1 expression, signaling pathways, promoter activity, mRNA and protein expression were assessed following treatment with pharmacological inhibitors and gene-specific siRNA knockdown. We found that CORM-3 mediated HO-1 induction via transcritional and translational processes. Furthermore, CORM-3-induced HO-1 expression was mediated by phosphorylation of several protein kinases, such as c-Src, Pyk2, protein kinase Cα (PKCα) and p42/p44 mitogen-activated protein kinase (MAPK), which were inhibited by respective pharmacological inhibitors or by gene-specific knockdown with siRNA transfections. Next, we found that CORM-3 sequentially activated the c-Src/Pyk2/PKCα/p42/p44 MAPK pathway, thereby up-regulating mRNA for the activator protein (AP)-1 components c-Jun and c-Fos; these effects were attenuated by an AP-1 inhibitor (Tanshinone IIA; TSIIA) and other relevant inhibitors. Moreover, CORM-3-induced upregulation of HO-1 attenuated the IL-1β-induced cell migration and matrix metallopeptidase-9 mRNA expression in RBA-1 cells. These effects were reversed by an matrix metalloproteinase (MMP)2/9 inhibitor or by transfection with HO-1 siRNA.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00387/fullcarbon monoxide releasing moleculesastrocytereactive oxygen speciesheme oxygenase-1inflammationsiRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chih-Chung Lin Chien-Chung Yang Chien-Chung Yang Li-Der Hsiao Ssu-Yu Chen Chuen-Mao Yang Chuen-Mao Yang Chuen-Mao Yang |
spellingShingle |
Chih-Chung Lin Chien-Chung Yang Chien-Chung Yang Li-Der Hsiao Ssu-Yu Chen Chuen-Mao Yang Chuen-Mao Yang Chuen-Mao Yang Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation Frontiers in Molecular Neuroscience carbon monoxide releasing molecules astrocyte reactive oxygen species heme oxygenase-1 inflammation siRNA |
author_facet |
Chih-Chung Lin Chien-Chung Yang Chien-Chung Yang Li-Der Hsiao Ssu-Yu Chen Chuen-Mao Yang Chuen-Mao Yang Chuen-Mao Yang |
author_sort |
Chih-Chung Lin |
title |
Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation |
title_short |
Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation |
title_full |
Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation |
title_fullStr |
Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation |
title_full_unstemmed |
Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation |
title_sort |
heme oxygenase-1 induction by carbon monoxide releasing molecule-3 suppresses interleukin-1β-mediated neuroinflammation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2017-11-01 |
description |
Neurodegenerative disorders and brain damage are initiated by excessive production of reactive oxygen species (ROS), which leads to tissue injury, cellular death and inflammation. In cellular anti-oxidant systems, heme oxygenase-1 (HO-1) is an oxidative-sensor protein induced by ROS generation or carbon monoxide (CO) release. CO releasing molecules (CORMs), including CORM-3, exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanisms of CORM-3-induced HO-1 expression and protection against interleukin (IL)-1β-induced inflammatory responses have not been fully elucidated in rat brain astrocytes (RBA-1). To study the regulation of CORM-3-induced HO-1 expression, signaling pathways, promoter activity, mRNA and protein expression were assessed following treatment with pharmacological inhibitors and gene-specific siRNA knockdown. We found that CORM-3 mediated HO-1 induction via transcritional and translational processes. Furthermore, CORM-3-induced HO-1 expression was mediated by phosphorylation of several protein kinases, such as c-Src, Pyk2, protein kinase Cα (PKCα) and p42/p44 mitogen-activated protein kinase (MAPK), which were inhibited by respective pharmacological inhibitors or by gene-specific knockdown with siRNA transfections. Next, we found that CORM-3 sequentially activated the c-Src/Pyk2/PKCα/p42/p44 MAPK pathway, thereby up-regulating mRNA for the activator protein (AP)-1 components c-Jun and c-Fos; these effects were attenuated by an AP-1 inhibitor (Tanshinone IIA; TSIIA) and other relevant inhibitors. Moreover, CORM-3-induced upregulation of HO-1 attenuated the IL-1β-induced cell migration and matrix metallopeptidase-9 mRNA expression in RBA-1 cells. These effects were reversed by an matrix metalloproteinase (MMP)2/9 inhibitor or by transfection with HO-1 siRNA. |
topic |
carbon monoxide releasing molecules astrocyte reactive oxygen species heme oxygenase-1 inflammation siRNA |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00387/full |
work_keys_str_mv |
AT chihchunglin hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT chienchungyang hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT chienchungyang hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT liderhsiao hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT ssuyuchen hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT chuenmaoyang hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT chuenmaoyang hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation AT chuenmaoyang hemeoxygenase1inductionbycarbonmonoxidereleasingmolecule3suppressesinterleukin1bmediatedneuroinflammation |
_version_ |
1716796295477198848 |