Inhibition of reactive oxygen species downregulates the MAPK pathway in rat spinal cord after limb ischemia reperfusion injury

Choi, Eun Kyung; Yeo, Ji‐Youn; Park, Chan Yoon; Na, Ho in; Lim, Jun Hee; Lee, Jeong Eun; Hong, Seong Wook; Park, Sung-Sik; Lim, Dong Gun; Kwak, Kyung Hwa

doi:10.1016/j.ijsu.2015.08.016

Cited by 22 publications

(16 citation statements)

References 38 publications

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“…ROS have been demonstrated to be an inducer or mediator of the activation of mitogen-activated protein kinase (MAPK) family members, including JNK, p38 and ERK1/2 (15). In addition, the MAPK signaling pathway has a significant role in the regulation of a number of cellular processes, including cell growth and proliferation, differentiation, and apoptosis (16).…”

Section: Eupatilin Activates Erk Jnk and P38 In 786-o Cellsmentioning

confidence: 99%

Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways

et al. 2016

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Abstract. Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades have significant roles in cell proliferation, survival, angiogenesis and metastasis of tumor cells. Eupatilin, one of the major compounds present in Artemisia species, has been demonstrated to have antitumor properties. However, the effect of eupatilin in renal cell carcinoma (RCC) remains to be elucidated. Therefore, the present study investigated the biological effects and mechanisms of eupatilin in RCC cell apoptosis. The results of the present study demonstrated that eupatilin significantly induced cell apoptosis and enhanced the production of reactive oxygen species (ROS) in 786-O cells. In addition, eupatilin induced phosphorylation of p38α (Thr180/Tyr182), extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase 1/2 (Thr183/Tyr185), and decreased the phosphorylation of PI3K and AKT in 786-O cells in a concentration-dependent manner. Furthermore, the ROS inhibitor N-acetyl-L-cysteine was able to rescue the MAPK activation and PI3K/AKT inhibition induced by eupatilin. Taken together, the results of the present study provide evidence that inhibition of eupatilin induces apoptosis in human RCC via ROS-mediated activation of the MAPK signaling pathway and inhibition of the PI3K/AKT signaling pathway. Thus, eupatilin may serve as a potential therapeutic agent for the treatment of human RCC.

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Section: Eupatilin Activates Erk Jnk and P38 In 786-o Cellsmentioning

confidence: 99%

Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways

et al. 2016

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“…At low concentrations, ROS functions as a messenger to enhance wound healing [ 9 ]. It targets survival pathways such as mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt [ 8 , 10 ]. ROS also targets hypoxia-inducible factor-1 (HIF-1), which upregulates gene expression of vascular endothelial growth factor (VEGF), an angiogenesis and vasculogenesis-inducing agent as well as a bone-metabolism cytokine that stimulates the differentiation and chemotactic migration of osteoblast precursor cells [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Hypothermia reduces VEGF-165 expression, but not osteogenic differentiation of human adipose stem cells under hypoxia

et al. 2017

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Cryotherapy is successfully used in the clinic to reduce pain and inflammation after musculoskeletal damage, and might prevent secondary tissue damage under the prevalent hypoxic conditions. Whether cryotherapy reduces mesenchymal stem cell (MSC) number and differentiation under hypoxic conditions, causing impaired callus formation is unknown. We aimed to determine whether hypothermia modulates proliferation, apoptosis, nitric oxide production, VEGF gene and protein expression, and osteogenic/chondrogenic differentiation of human MSCs under hypoxia. Human adipose MSCs were cultured under hypoxia (37°C, 1% O2), hypothermia and hypoxia (30°C, 1% O2), or control conditions (37°C, 20% O2). Total DNA, protein, nitric oxide production, alkaline phosphatase activity, gene expression, and VEGF protein concentration were measured up to day 8. Hypoxia enhanced KI67 expression at day 4. The combination of hypothermia and hypoxia further enhanced KI67 gene expression compared to hypoxia alone, but was unable to prevent the 1.2-fold reduction in DNA amount caused by hypoxia at day 4. Addition of hypothermia to hypoxic cells did not alter the effect of hypoxia alone on BAX-to-BCL-2 ratio, alkaline phosphatase activity, gene expression of SOX9, COL1, or osteocalcin, or nitric oxide production. Hypothermia decreased the stimulating effect of hypoxia on VEGF-165 gene expression by 6-fold at day 4 and by 2-fold at day 8. Hypothermia also decreased VEGF protein expression under hypoxia by 2.9-fold at day 8. In conclusion, hypothermia decreased VEGF-165 gene and protein expression, but did not affect differentiation, or apoptosis of MSCs cultured under hypoxia. These in vitro results implicate that hypothermia treatment in vivo, applied to alleviate pain and inflammation, is not likely to harm early stages of callus formation.

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“…Oxidative injury and apoptosis play the most important roles in central nervous system neurological disorders, including SCI (Liu and Xu, 2012). Reactive oxygen species (ROS), such as hydrogen peroxide, superoxide, and hydroxyl radicals, increased significantly within hours after SCI (Choi et al, 2015;Zhang et al, 2016). Among the antioxidative mechanisms, one of the major adaptive responses in the central nervous system is mediated by Nrf2.…”

Section: Discussionmentioning

confidence: 99%

Treatment With 2-BFI Attenuated Spinal Cord Injury by Inhibiting Oxidative Stress and Neuronal Apoptosis via the Nrf2 Signaling Pathway

Lin

Zhu

et al. 2019

Front. Cell. Neurosci.

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Previous reports showed that 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) has antioxidant, anti-inflammatory and anti-apoptotic effects on neuroprotection in numerous disorders. However, the precise mechanisms remain elusive. The nuclear factor c factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an important and essential role in the antioxidant and anti-inflammatory responses of the cell. Therefore, the purpose of this study was to investigate the potential neuroprotective effects of 2-BFI in a rat model of spinal cord injury (SCI) and to determine whether its neuroprotective effects are associated with the activation of Nrf2. To test this hypothesis, we examined the potential roles of 2-BFI in SCI models which were established in rats using a clip-compression injury method. Our results showed that treatment with 2-BFI twice daily improved locomotion recovery from SCI, which increased Nrf2 expression in both neurons and astrocytes, meanwhile, the level of heme oxygenase-1 (HO-1) also significantly enhanced. In addition, after the treatment with 2-BFI increased levels of superoxidase dismutase (SOD) and glutathione peroxidase (GPx) indicated the antioxidant effect of the drug. Furthermore, the upregulation of Bcl-2 and downregulation of Bax and caspase-3 implied antiapoptotic effects on neuroprotection of 2-BFI, which were verified by the Fluoro-Jade B (FJB) staining and TUNEL staining. Collectively, these results add to a growing body of evidence supporting that 2-BFI may attenuate SCI mediated by activation of the Nrf2/HO-1 signaling pathway.

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Inhibition of reactive oxygen species downregulates the MAPK pathway in rat spinal cord after limb ischemia reperfusion injury

Cited by 22 publications

References 38 publications

Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways

Eupatilin induces human renal cancer cell apoptosis via ROS-mediated MAPK and PI3K/AKT signaling pathways

Hypothermia reduces VEGF-165 expression, but not osteogenic differentiation of human adipose stem cells under hypoxia

Treatment With 2-BFI Attenuated Spinal Cord Injury by Inhibiting Oxidative Stress and Neuronal Apoptosis via the Nrf2 Signaling Pathway

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