Pomalidomide ameliorates H2O2-induced oxidative stress injury and cell death in rat primary cortical neuronal cultures by inducing anti-oxidative and anti-apoptosis effects

Yan Rou Tsai, Cheng Fu Chang, Jing Huei Lai, John Chung Che Wu, Yen Hua Chen, Shuo Jhen Kang, Barry J. Hoffer, David Tweedie, Weiming Luo, Nigel H. Greig, Yung Hsiao Chiang, Kai Yun Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2 O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2 O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 19 2018

Fingerprint

Oxidative stress
apoptosis
Cell death
Cell culture
death
rats
Rats
Oxidative Stress
Cell Death
Apoptosis
Oxygen
Brain
Wounds and Injuries
oxygen
Reactive Oxygen Species
Administrative data processing
Neuroprotective Agents
disorders
brain damage
damage

Keywords

  • Ischemia
  • Neurodegeneration
  • Neuroprotection
  • Oxidative stress
  • Pomalidomide
  • Stroke

Cite this

Pomalidomide ameliorates H2O2-induced oxidative stress injury and cell death in rat primary cortical neuronal cultures by inducing anti-oxidative and anti-apoptosis effects. / Tsai, Yan Rou; Chang, Cheng Fu; Lai, Jing Huei; Wu, John Chung Che; Chen, Yen Hua; Kang, Shuo Jhen; Hoffer, Barry J.; Tweedie, David; Luo, Weiming; Greig, Nigel H.; Chiang, Yung Hsiao; Chen, Kai Yun.

In: International Journal of Molecular Sciences, Vol. 19, No. 10, 19.10.2018.

Research output: Contribution to journalArticle

Tsai, Yan Rou ; Chang, Cheng Fu ; Lai, Jing Huei ; Wu, John Chung Che ; Chen, Yen Hua ; Kang, Shuo Jhen ; Hoffer, Barry J. ; Tweedie, David ; Luo, Weiming ; Greig, Nigel H. ; Chiang, Yung Hsiao ; Chen, Kai Yun. / Pomalidomide ameliorates H2O2-induced oxidative stress injury and cell death in rat primary cortical neuronal cultures by inducing anti-oxidative and anti-apoptosis effects. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 10.
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abstract = "{\circledC} 2018 by the authors. Licensee MDPI, Basel, Switzerland. Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2 O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2 O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.",
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T1 - Pomalidomide ameliorates H2O2-induced oxidative stress injury and cell death in rat primary cortical neuronal cultures by inducing anti-oxidative and anti-apoptosis effects

AU - Tsai, Yan Rou

AU - Chang, Cheng Fu

AU - Lai, Jing Huei

AU - Wu, John Chung Che

AU - Chen, Yen Hua

AU - Kang, Shuo Jhen

AU - Hoffer, Barry J.

AU - Tweedie, David

AU - Luo, Weiming

AU - Greig, Nigel H.

AU - Chiang, Yung Hsiao

AU - Chen, Kai Yun

PY - 2018/10/19

Y1 - 2018/10/19

N2 - © 2018 by the authors. Licensee MDPI, Basel, Switzerland. Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2 O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2 O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.

AB - © 2018 by the authors. Licensee MDPI, Basel, Switzerland. Due to its high oxygen demand and abundance of peroxidation-susceptible lipid cells, the brain is particularly vulnerable to oxidative stress. Induced by a redox state imbalance involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system, oxidative stress plays a central role in a common pathophysiology that underpins neuronal cell death in acute neurological disorders epitomized by stroke and chronic ones such as Alzheimer’s disease. After cerebral ischemia, for example, inflammation bears a key responsibility in the development of permanent neurological damage. ROS are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Using H2 O2-treated rat primary cortical neuronal cultures, we found POM displayed neuroprotective effects against oxidative stress and cell death that associated with changes in the nuclear factor erythroid derived 2/superoxide dismutase 2/catalase signaling pathway. POM also suppressed nuclear factor kappa-light-chain-enhancer (NF-κB) levels and significantly mitigated cortical neuronal apoptosis by regulating Bax, Cytochrome c and Poly (ADP-ribose) polymerase. In summary, POM exerted neuroprotective effects via its anti-oxidative and anti-inflammatory actions against H2 O2-induced injury. POM consequently represents a potential therapeutic agent against brain damage and related disorders and warrants further evaluation.

KW - Ischemia

KW - Neurodegeneration

KW - Neuroprotection

KW - Oxidative stress

KW - Pomalidomide

KW - Stroke

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