scholarly journals P27 Protects Neurons from Ischemic Damage by Suppressing Oxidative Stress and Increasing Autophagy in the Hippocampus

2020 ◽  
Vol 21 (24) ◽  
pp. 9496
Author(s):  
Woosuk Kim ◽  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Yeo Sung Yoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Ht22 Cells ◽  
H2o2 Treatment ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 μM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 μM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.

scholarly journals Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1827 ◽  
Author(s):  
Hyun Jung Kwon ◽  
Duk-Soo Kim ◽  
Woosuk Kim ◽  
Hyo Young Jung ◽  
Yeon Hee Yu ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Concentration Dependent Manner ◽  
H2o2 Treatment ◽  
Interacting Protein

Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the C-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H2O2-induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H2O2 treatment in HT22 cells. Ischemia–reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus.

scholarly journals Tat-Endophilin A1 Fusion Protein Protects Neurons from Ischemic Damage in the Gerbil Hippocampus: A Possible Mechanism of Lipid Peroxidation and Neuroinflammation Mitigation as Well as Synaptic Plasticity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 357
Author(s):  
Hyo Young Jung ◽  
Hyun Jung Kwon ◽  
Woosuk Kim ◽  
In Koo Hwang ◽  
Goang-Min Choi ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Synaptic Plasticity ◽  
Prostaglandin F2α ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Forebrain Ischemia ◽  
Ht22 Cells ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

The present study explored the effects of endophilin A1 (SH3GL2) against oxidative damage brought about by H2O2 in HT22 cells and ischemic damage induced upon transient forebrain ischemia in gerbils. Tat-SH3GL2 and its control protein (Control-SH3GL2) were synthesized to deliver it to the cells by penetrating the cell membrane and blood–brain barrier. Tat-SH3GL2, but not Control-SH3GL2, could be delivered into HT22 cells in a concentration- and time-dependent manner and the hippocampus 8 h after treatment in gerbils. Tat-SH3GL2 was stably present in HT22 cells and degraded with time, by 36 h post treatment. Pre-incubation with Tat-SH3GL2, but not Control-SH3GL2, significantly ameliorated H2O2-induced cell death, DNA fragmentation, and reactive oxygen species formation. SH3GL2 immunoreactivity was decreased in the gerbil hippocampal CA1 region with time after ischemia, but it was maintained in the other regions after ischemia. Tat-SH3GL2 treatment in gerbils appreciably improved ischemia-induced hyperactivity 1 day after ischemia and the percentage of NeuN-immunoreactive surviving cells increased 4 days after ischemia. In addition, Tat-SH3GL2 treatment in gerbils alleviated the increase in lipid peroxidation as assessed by the levels of malondialdehyde and 8-iso-prostaglandin F2α and in pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6; while the reduction of protein levels in markers for synaptic plasticity, such as postsynaptic density 95, synaptophysin, and synaptosome associated protein 25 after transient forebrain ischemia was also observed. These results suggest that Tat-SH3GL2 protects neurons from oxidative and ischemic damage by reducing lipid peroxidation and inflammation and improving synaptic plasticity after ischemia.

scholarly journals Neuroprotective Effects of Purpurin Against Ischemic Damage via Anti-inflammatory and MAPK Pathway

2021 ◽  
Author(s):  
Woosuk Kim ◽  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Yeo Sung Yoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mapk Pathway ◽  
Ischemic Damage ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Protein Levels ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Anti Inflammatory

Abstract Purpurin has various effects, including anti-inflammatory effects, and can efficiently cross the blood-brain barrier. In the present study, we investigated the effects of purpurin on oxidative stress in HT22 cells and ischemic damage in the hippocampal CA1 region of gerbils. Oxidative stress induced by H2O2 was significantly ameliorated by treatment with purpurin, based on changes in cell death, DNA fragmentation, formation of reactive oxygen species, and apoptosis (Bcl-2)/antiapoptosis (Bax)-related protein levels. In addition, treatment with purpurin significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK), and p38 signaling in HT22 cells. Transient forebrain ischemia in gerbils led to a significant increase in locomotor activity 1 day after ischemia and significant decrease in number of surviving cells in the CA1 region 4 days after ischemia. Administration of purpurin reduced the travel distance 1 day after ischemia and increased the number of NeuN-immunoreactive neurons in the hippocampal CA1 region of the dentate gyrus 4 days after ischemia. Purpurin treatment significantly decreased microglial activation in the hippocampal CA1 region 4 days after ischemia and ameliorated the ischemia-induced increases in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α 6 h after ischemia. In addition, purpurin significantly alleviated the ischemia-induced phosphorylation of JNK, ERK, and p38 in the hippocampus 1 day after ischemia. These results suggest that purpurin has neuroprotective potential to reduce inflammatory processes and the phosphorylation of JNK, ERK, and p38 in the hippocampus.

scholarly journals Neuroprotective Effect of Gallocatechin Gallate on Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1387
Author(s):  
Do Hwi Park ◽  
Jun Yeon Park ◽  
Ki Sung Kang ◽  
Gwi Seo Hwang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Glutamate Excitotoxicity ◽  
Nuclear Condensation ◽  
Epicatechin Gallate ◽  
Ht22 Cells ◽  
Gallocatechin Gallate

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. Glutamate is a neurotransmitter that nerve cells use to send signals. However, the excess accumulation of glutamate can cause excitotoxicity in the central nervous system. In this study, we deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. Cellular antioxidant activity was determined using the 1,1-diphenyl-picryl hydrazyl (DPPH) assay and 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) staining. Furthermore, the levels of intracellular calcium (Ca2+) as well as nuclear condensation and protein expression related to neuronal damage were assessed. All five catechins (epigallocatechin gallate, gallocatechin gallate (GCG), gallocatechin, epicatechin gallate, and epicatechin) showed strong antioxidant effects. Among them, GCG exhibited the highest neuroprotective effect against glutamate excitotoxicity and was used for further mechanistic studies. The glutamate-induced increase in intracellular Ca2+ was reduced after GCG treatment. Moreover, GCG reduced nuclear condensation and the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) involved in cell death. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and also the inhibition of phosphorylation of ERK and JNK. Furthermore, the antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells.

The Bcl-2 proteins Noxa and Bcl-xL co-ordinately regulate oxidative stress-induced apoptosis

2012 ◽  
Vol 444 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Colins O. Eno ◽  
Guoping Zhao ◽  
Kristen E. Olberding ◽  
Chi Li
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Myeloid Cell ◽  
Cell Leukaemia ◽  
Dependent Manner ◽  
Embryonic Fibroblasts ◽  
H2o2 Treatment ◽  
Apoptotic Activity ◽  
Induced Apoptosis

Because the detailed molecular mechanisms by which oxidative stress induces apoptosis are not completely known, we investigated how the complex Bcl-2 protein network might regulate oxidative stress-induced apoptosis. Using MEFs (mouse embryonic fibroblasts), we found that the endogenous anti-apoptotic Bcl-2 protein Bcl-xL prevented apoptosis initiated by H2O2. The BH3 (Bcl-2 homology 3)-only Bcl-2 protein Noxa was required for H2O2-induced cell death and was the single BH3-only Bcl-2 protein whose pro-apoptotic activity was completely antagonized by endogenous Bcl-xL. Upon H2O2 treatment, Noxa mRNA displayed the greatest increase among BH3-only Bcl-2 proteins. Expression levels of the anti-apoptotic Bcl-2 protein Mcl-1 (myeloid cell leukaemia sequence 1), the primary binding target of Noxa, were reduced in H2O2-treated cells in a Noxa-dependent manner, and Mcl-1 overexpression was able to prevent H2O2-induced cell death in Bcl-xL-deficient MEF cells. Importantly, reduction of the expression of both Mcl-1 and Bcl-xL caused spontaneous cell death. These studies reveal a signalling pathway in which H2O2 activates Noxa, leading to a decrease in Mcl-1 and subsequent cell death in the absence of Bcl-xL expression. The results of the present study indicate that both anti- and pro-apoptotic Bcl-2 proteins co-operate to regulate oxidative stress-induced apoptosis.

scholarly journals Methane-Rich Saline Alleviates CA/CPR Brain Injury by Inhibiting Oxidative Stress, Microglial Activation-Induced Inflammatory Responses, and ER Stress-Mediated Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ruixia Cui ◽  
Sinan Liu ◽  
Cong Wang ◽  
Tong Liu ◽  
Jie Ren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Arrest ◽  
Brain Injury ◽  
Er Stress ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Brain injury induced by cardiac arrest/cardiopulmonary resuscitation (CA/CPR) is the leading cause of death among patients who have recovery of spontaneous circulation (ROSC). Inflammatory response, apoptosis, and oxidative stress are proven pathological mechanisms implicated in neuronal damage. Methane-rich saline (MRS) has been proven that exerts a beneficial protectiveness impact in several models of ischemia-reperfusion injury. The goal of this paper is to ascertain the role of MRS in CA/CPR-induced brain injury and its potential mechanisms. The tracheal intubation of Sprague-Dawley (SD) rats was clamped for 6 min to establish an asphyxiating cardiac arrest model. After that, chest compressions were applied; then, MRS or saline was administered immediately post-ROSC, the rats were sacrificed, and brain tissue was collected at the end of 6 hours. We observed that MRS treatment attenuated neuronal damage in the hippocampal CA1 region by inhibiting microglial activation, leading to a decrease in the overexpression of proinflammatory cytokines such as TNF-α, IL-6, and iNOS. The results also illustrated that MRS treatment diminished apoptosis in the hippocampal CA1 region , reduced the expression of apoptosis-associated proteins Bax and cleaved caspase9, and increased Bcl-2 expression, as well as inhibited the expression of endoplasmic reticulum (ER) stress pathway-related proteins GRP78, ATF4, and CHOP. Further findings showed that MRS treatment significantly attenuated hippocampal ROS and MDA levels and increased GSH and SOD antioxidant factor levels, which indicated that MRS treatment could inhibit oxidative stress. Our results suggest that MRS exerts a protective effect against CA/CPR brain injury, by inhibiting oxidative stress, microglial activation-induced inflammatory responses, and ER stress-mediated apoptosis.

scholarly journals Probucol Attenuates Oxidative Stress, Energy Starvation, and Nitric Acid Production Following Transient Forebrain Ischemia in the Rat Hippocampus

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Abdulhakeem A. Al-Majed
Keyword(s):  
Oxidative Stress ◽  
Neuronal Damage ◽  
Lipid Lowering ◽  
Albino Rats ◽  
Forebrain Ischemia ◽  
Energy Depletion ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Oxidative stress and energy depletion are believed to participate in hippocampal neuronal damage after forebrain ischemia. This study has been initiated to investigate the potential neuroprotective effects of probucol, a lipid-lowering drug with strong antioxidant properties, against transient forebrain ischemia-induced neuronal damage and biochemical abnormalities in rat hippocampal CA1 region. Adult male Wistar albino rats were subjected to forebrain ischemia and injected with probucol for the next 7 successive days, and compared to controls. Forebrain ischemia resulted in a significant decrease in the number of intact neurons (77%), glutathione (GSH), and adenosine triphosphate (ATP), and a significant increase in thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite, (NOx) production in hippocampal tissues. The administration of probucol attenuated forebrain ischemia-induced neuronal damage, manifested as a complete reversal of the decrease in the number of intact neurons, ATP and GSH and the increase in TBARS and NOxin hippocampal tissues. This study demonstrates that probucol treatment abates forebrain ischemia-induced hippocampal neuronal loss, energy depletion, and oxidative stress in hippocampal CA1 region. Thus, probucol could be a promising neuroprotective agent in the treatment of forebrain ischemia.

scholarly journals Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells

2019 ◽  
Vol 43 (2) ◽  
pp. 326-334 ◽  
Author(s):  
Dong Hoi Kim ◽  
Dae Won Kim ◽  
Bo Hyun Jung ◽  
Jong Hun Lee ◽  
Heesu Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Ginsenoside Rb2

scholarly journals Neuroprotective Effects of Tetrahydrocurcumin against Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 144 ◽  
Author(s):  
Chang-Hyun Park ◽  
Ji Hoon Song ◽  
Su-Nam Kim ◽  
Ji Hwan Lee ◽  
Hae-Jeung Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protein Kinases ◽  
Apoptotic Cell ◽  
Curcuma Longa ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

In the central nervous system, glutamate is a major excitable neurotransmitter responsible for many cellular functions. However, excessive levels of glutamate induce neuronal cell death via oxidative stress during acute brain injuries as well as chronic neurodegenerative diseases. The present study was conducted to examine the effect of tetrahydrocurcumin (THC), a major secondary metabolite of curcumin, and its possible mechanism against glutamate-induced cell death. We prepared THC using curcumin isolated from Curcuma longa (turmeric) and demonstrated the protective effect of THC against glutamate-induced oxidative stress in HT22 cells. THC abrogated glutamate-induced HT22 cell death and showed a strong antioxidant effect. THC also significantly reduced intracellular calcium ion increased by glutamate. Additionally, THC significantly reduced the accumulation of intracellular oxidative stress induced by glutamate. Furthermore, THC significantly diminished apoptotic cell death indicated by annexin V-positive in HT22 cells. Western blot analysis indicated that the phosphorylation of mitogen-activated protein kinases including c-Jun N-terminal kinase, extracellular signal-related kinases 1/2, and p38 by glutamate was significantly diminished by treatment with THC. In conclusion, THC is a potent neuroprotectant against glutamate-induced neuronal cell death by inhibiting the accumulation of oxidative stress and phosphorylation of mitogen-activated protein kinases.

scholarly journals Honokiol ameliorates radiation-induced brain injury via the activation of SIRT3

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096399
Author(s):  
Guixiang Liao ◽  
Zhihong Zhao ◽  
Hongli Yang ◽  
Xiaming Li
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Tnf Α ◽  
Radiation Induced ◽  
Cox 2

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

Sign in / Sign up

Export Citation Format

Share Document