Inhibition of ROS-induced p38MAPK and ERK activation in microglia by acupuncture relieves neuropathic pain after spinal cord injury in rats

Choi, Doo C.; Lee, Jee Y.; Lim, Eic Ju; Baik, Hee Jung; Oh, Tae Hwan; Yune, Tae Young

doi:10.1016/j.expneurol.2012.05.014

Cited by 114 publications

(103 citation statements)

References 67 publications

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“…Several studies reported that AtP receptor purinergic receptors 4 (P2X4R) and p38-mitogen-activated protein kinase (p38MAPK) were significantly increased after microglia activation as a result of peripheral nerve injury 24,26 . Reactive oxygen species produced after injury-induced p38MAPK and extracellular regulated protein kinases (ERK) activation in microglia, and mediated mechanical allodynia and thermal hyperalgesia 27 . P2X4R also mediates synthesis and release of bDNF in the microglia in a calcium-and p38MAPK-dependent manner 28 .…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-Rich Saline Attenuated Neuropathic Pain by Reducing Oxidative Stress

Chen

Zhou

et al. 2013

Can. J. Neurol. Sci.

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Reactive oxygen species (RoS) are involved in the development of pains in various conditions, including neuropathic and inflammatory pain [1][2][3][4][5] . Park et al reported increased RoS in the spinal cord of rats after peripheral nerve injury 6 . others found that treatment with RoS scavengers phenyl Ntert-butylnitrone (PbN), 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tEMPoL), 5,5-dimethylpyrroline -N-oxide (DMPo) or vitamin E could temporarily reverse the allodynia developed after nerve ligation in rats 2,7,8 . the function mechanisms of RoS scavenger, like that of PbN-induced analgesic effect, are reported to be mediated mainly via spinal mechanisms 2 .ABSTRACT: Background: Reactive oxygen species (RoS) are often associated with persistent pains such as neuropathic and inflammatory pain. Hydrogen gas can reduce RoS and alleviate cerebral, myocardial, and hepatic ischemia/reperfusion injuries. in the present study, we aim to investigate whether hydrogen-rich saline can reduce neuropathic pain in a rat model of chronic constriction injury (CCi). Methods: thirty SD rats were randomly divided into three groups: sham group was administered sodium chloride by intrathecal injection (n=10); control groups underwent CCi surgery and were administered sodium chloride by intrathecal injection (n=10); vehicle group underwent CCi surgery and was administered hydrogen-rich saline by intrathecal injection (n=10). Drugs were administered in the dose of 100ul/kg once a day at 0.5 hours before and 1-7 day after CCi surgery. the mechanical thresholds were tested at one day before and 3-14 day after CCi surgery. Results: We found that hydrogen-rich saline significantly elevated the mechanical thresholds of neuropathic pain compared to vehicle (physiologic saline) control in CCi rats (p<0.05); it also decreased the levels of myeloperoxidase, maleic dialdehyde, and protein carbonyl in spinal cord by 7 days post-chronic constriction injury(p<0.05). in addition, hydrogen-rich saline also suppressed the expression of p38-mitogen-activated protein kinase (p38MAPK) and brain-derived neurotrophic factor (bDNF) in the spinal cord by 7 days post-chronic constriction injury (p<0.01, p<0.01, respectively), but had no effect on P2X4R (p>0.05), an AtP receptor. Conclusion: intrathecal injection of hydrogen-rich saline can decrease oxidative stress and the expression of p38MAPK and bDNF that may contribute to the elevated threshold of neuropathic pain in rat CCi model. RÉSUMÉ:Le salin riche en hydrogène atténue la douleur névropathique en réduisant le stress oxydatif. Contexte : Les espèces réactives oxygénées (RoS) sont souvent associées à la douleur persistante comme la douleur névropathique et la douleur inflammatoire. Le gaz hydrogène peut réduire les RoS et soulager le dommage dû à l'ischémie/la reperfusion au niveau cérébral, myocardique et hépatique. Le but de cette étude était de déterminer si le salin riche en hydrogène peut réduire la douleur névropathique chez un modèle de lésion par constriction chronique (LCC) chez le rat. ...

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Section: Discussionmentioning

confidence: 99%

Hydrogen-Rich Saline Attenuated Neuropathic Pain by Reducing Oxidative Stress

Chen

Zhou

et al. 2013

Can. J. Neurol. Sci.

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“…The dose of drugs used in the experiment was chosen based on previous research. 34,35 Intraspinal injection was performed as previously described. 36 In brief, SP600125 (5 lL) or MnTBAP (10 lL) was injected into the lesion epicenter (1.5 mm depth) using a pulled glass capillary pipette micropipette attached to a Hamilton syringe connected to a micromanipulator.…”

Section: Drug Administrationmentioning

confidence: 99%

Valproic Acid Protects Motor Neuron Death by Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress-Mediated Cytochrome C Release after Spinal Cord Injury

Lee

Maeng

Kang

et al. 2014

Journal of Neurotrauma

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Both oxidative stress and endoplasmic reticulum (ER) stress are known to contribute to secondary injury, ultimately leading to cell death after spinal cord injury (SCI). Here, we showed that valproic acid (VPA) reduced cell death of motor neurons by inhibiting cytochrome c release mediated by oxidative stress and ER stress after SCI. After SCI, rats were immediately injected with VPA (300 mg/kg) subcutaneously and further injected every 12 h for an indicated time period. Motor neuron cell death at an early time after SCI was significantly attenuated by VPA treatment. Superoxide anion (O2-) production and inducible NO synthase (iNOS) expression linked to oxidative stress was increased after injury, which was inhibited by VPA. In addition, VPA inhibited c-Jun N-terminal kinase (JNK) activation, which was activated and peaked at an early time after SCI. Furthermore, JNK activation and c-Jun phosphorylation were inhibited by a broad-spectrum reactive oxygen species (ROS) scavenger, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), indicating that ROS including O2- increased after SCI probably contribute to JNK activation. VPA also inhibited cytochrome c release and caspase-9 activation, which was significantly inhibited by SP600125, a JNK inhibitor. The levels of phosphorylated Bim and Mcl-1, which are known as downstream targets of JNK, were significantly reduced by SP600125. On the other hand, VPA treatment inhibited ER stress-induced caspase-12 activation, which is activated in motor neurons after SCI. In addition, VPA increased the Bcl-2/Bax ratio and inhibited CHOP expression. Taken together, our results suggest that cell death of motor neurons after SCI is mediated through oxidative stress and ER stress-mediated cytochrome c release and VPA-inhibited cytochrome c release by attenuating ROS-induced JNK activation followed by Mcl-1 and Bim phosphorylation and ER stress-coupled CHOP expression.

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“…In addition, the authors hypothesized that singlet oxygen is the dominant ROS. A previous study also revealed that antioxidants may effectively restrain ROS generation and apoptosis caused by UVA (28). The generated ROS activates the upstream activating agent and apoptosis signal conditioning kinase 1 (AsKI) of p38 and c-Jun N-terminal kinase, so as to activate p38, indicating that ROS-ASKI-p38MAPK pathway is an important signal transduction pathway in the carcinogenic effects of ultraviolet light (29).…”

Section: Discussionmentioning

confidence: 95%

Salvianolic acid B suppresses cell proliferation and induces apoptosis in osteosarcoma through p38-mediated reactive oxygen species generation

et al. 2017

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Abstract. The present study aimed to investigate the potential anticancer effect and mechanisms of salvianolic acid B on osteosarcoma. Salvianolic acid B suppressed osteosarcoma cell proliferation and induced apoptosis in the osteosarcoma MG63 cell line, and activated the expressions of cleaved caspase-3, phosphorylated-tumor protein (p)38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated-p53 (p-p53) proteins in the MG63 cells. Additionally, Salvianolic acid B also increased the level of reactive oxygen species (ROS) generation in the MG63 cells. The silencing of p38 expression inhibited the anticancer effect of salvianolic acid B on the levels of cell proliferation, p-p53 protein expression and ROS generation level in the MG63 cells. All these data supported the hypothesis that the anticancer effect of salvianolic acid B includes the suppression of cell proliferation and induces apoptosis in MG63 cells, and that p38 is important in the anticancer effect of salvianolic acid B on osteosarcoma cells due to the direct regulation of ROS generation. These data suggest that salvianolic acid B is important in the proliferation of osteosarcoma cells due to the direct regulation of p38-mediated ROS signaling. IntroductionOsteosarcoma is a type of primary malignant tumor that exhibits the highest morbidity of all neoplasms in the human skeletal system, and often presents in the metaphysis of the long tubal bones (1). Osteosarcoma often affects young people between the age of 20 and 30 years old. The mortality rate is high (2) and ~20% of patients exhibit pulmonary metastasis prior to diagnosis. Subsequent to diagnosis, the majority of patients succumb to the disease within 2 years (2). At present, there are no effective therapeutic treatments for early osteosarcoma (3). Therefore, it is important to investigate the causes of osteosarcoma occurrence, development and invasion, the mechanisms of osteosarcoma oncogenesis, and to identify effective diagnostic and therapeutic techniques. The development of gene therapy has created novel research targets in oncotherapy, including the identification of a target gene (4).Mitogen-activated protein kinase (MAPK) is the one of the most important types of signal conduction pathway in humans, and interacts with multiple signaling pathways (5). The tumor protein (p)38 MAPK pathway is activated through phosphotyrosine and threonine and inflammatory and growth factors, and activates downstream transcription factors on target genes, increases the initiation of cancer cell development, promotes protein synthesis, regulates cell surface receptors and regulates the invasion and transfer of tumor cells (6).Reactive oxygen species (ROS) are secondary products in the process of aerobic metabolism and include oxygen ions, peroxide and oxygen radical molecules (7). The increase in the level of intracellular ROS may promote cellular proliferation and differentiation to some extent. However, excessive levels of ROS results in damage to lipids, proteins and DNA, destroying numerous nor...

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Inhibition of ROS-induced p38MAPK and ERK activation in microglia by acupuncture relieves neuropathic pain after spinal cord injury in rats

Cited by 114 publications

References 67 publications

Hydrogen-Rich Saline Attenuated Neuropathic Pain by Reducing Oxidative Stress

Hydrogen-Rich Saline Attenuated Neuropathic Pain by Reducing Oxidative Stress

Valproic Acid Protects Motor Neuron Death by Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress-Mediated Cytochrome C Release after Spinal Cord Injury

Salvianolic acid B suppresses cell proliferation and induces apoptosis in osteosarcoma through p38-mediated reactive oxygen species generation

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