Antioxidative and Antiapoptotic Effects of Delta-Opioid Peptide [D-Ala2, D-Leu5] Enkephalin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Fu, Danyun; Liu, Haitong; Li, Shitong; Chen, Lianhua; Yao, Junyan

doi:10.3389/fnins.2017.00603

Cited by 15 publications

(10 citation statements)

References 24 publications

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“…The precise molecular mechanisms responsible for the detrimental effects of SCII remain elusive; however, it is generally accepted that the SCII-induced locomotor deficits and tissue damage are in part attributable to the elevated oxidative stress, apoptotic signaling, as well as neuroinflammation that take place following SCII [6-9]. To date, there still lacks effective treatment for SCII, but alternative approaches exist that can protect against SCII through anti-inflammatory, antioxidative, or antiapoptotic activities [10, 11, 25]. In the current paper, we presented evidence that lycopene, a natural compound in tomato and many other red fruits and vegetables, improved SCII-induced neurological disabilities and suppressed neuroinflammation, thereby exerting neuroprotective functions.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression

et al. 2019

Neuroimmunomodulation

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Objective: Spinal cord ischemia/reperfusion injury (SCII) is a devastating complication following thoracoabdominal aortic surgeries, often leading to severe neurological deficits. We sought to examine the effects of lycopene, a naturally existing carotenoid with anti-inflammatory properties, in the treatment against SCII. Methods: Rats were assigned into four treatment groups: Sham (sham operation), SCII (SCII-induction), LY25, and LY50 (lycopene treatment at 25 or 50 mg/kg following SCII induction, respectively). Results: Lycopene treatment improved the recovery of neurological functions following SCII and suppressed the neuronal cell death and neuroinflammation at 14 days after SCII. Furthermore, Western blot assay revealed that lycopene treatment attenuated the SCII-induced increase in the protein levels of cyclooxygenase-2 (COX-2), nuclear factor-κB, and activate protein-1, as well as the reduction of heme oxygenase-1. Conclusion: Lycopene exerted neuroprotective functions in SCII and inhibited SCII-elicited neuroinflammation via COX-2 suppression.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression

et al. 2019

Neuroimmunomodulation

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“…In recent years, the neuroprotective effects of DOR have received increasing attention. Pharmacological studies found that DOR activation by DADLE significantly promoted neuronal survival in multiple animal models 15,26 –28 . Studies in cultured neurons suggested that DOR-mediated neuroprotection was associated with ionic homeostasis, cellular transcription, antioxidative stress, and antiapoptosis 29,30 .…”

Section: Discussionmentioning

confidence: 99%

Delta Opioid Peptide [d-Ala2, d-Leu5] Enkephalin (DADLE) Exerts a Cytoprotective Effect in Astrocytes Exposed to Oxygen-Glucose Deprivation by Inducing Autophagy

et al. 2019

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Astrocytes protection and functional regulation are important strategies to protect against neuronal damage caused by ischemia. Activation of the delta opioid receptor (DOR) could reduce astrocytes damage, although the mechanism remains unclear. The present study aimed to test the effect of DOR activation on autophagy in astrocytes exposed to oxygen-glucose deprivation (OGD), and to further investigate whether this effect has a protective effect on astrocytes. Primary cultured rat cortical astrocytes were treated with various doses of [d-Ala2, d-Leu5]-Enkephalin (DADLE, a selective DOR agonist) followed by 6 h OGD. Cell viability was evaluated by CCK-8 assay and lactate dehydrogenase release. Autophagic vacuole was analyzed with LC3 immunofluorescent staining. The levels of autophagy and apoptosis-related proteins were analyzed by western blot. Results demonstrated that treatment with 10 nM DADLE was sufficient to increase cell viability and induced autophagy in astrocytes. The DADLE-induced autophagy displayed a cytoprotective effect on astrocytes. Inhibition of autophagy by 3-methyladenine (3-MA, an autophagy inhibitor) reversed the protective effect of DADLE. Naltrindole (a DOR antagonist) only partially antagonized the role of DADLE, which indicated that DADLE might have a cytoprotective mechanism independent of DOR. Further results showed that DADLE significantly enhanced the level of Bcl-2 protein and reduced the level of Bax protein in astrocytes exposed to OGD. Our results suggest a novel mechanism in which DADLE induces autophagy in astrocytes and exerts cytoprotective effects by inhibiting apoptosis.

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“…The supernatant was collected and protein concentration was determined using a BCA protein assay kit (Beyotime, Shanghai, China). Superoxide dismutase (SOD), GSH, and GSSG levels were measured using a SOD, GSH, and GSSG Assay Kit (Nanjing Jiancheng Bioengineering Institute, Nanjing, China), performed according to the manufacturer’s instruction ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

Leptin Maintained Zinc Homeostasis Against Glutamate-Induced Excitotoxicity by Preventing Mitophagy-Mediated Mitochondrial Activation in HT22 Hippocampal Neuronal Cells

Jin

Hóng

2018

Front. Neurol.

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Developmental seizure-induced long-term neuronal hyperexcitation is partially mediated by regenerative mossy fiber sprouting in hippocampus. Yet, there are no effective drugs available to block this pathological process. Recently, leptin has been shown to prevent the sprouting of hippocampal mossy fibers and abnormalities in the neurobehavioral parameters. However, their underlying molecular mechanisms are largely unknown. The purpose of this study was to determine the effect of glutamate on the parameters of zinc homeostasis, mitochondrial functions, and mitophagy regulating factors, as well as to investigate the protective effects of leptin against cytotoxicity of glutamate in murine HT22 hippocampal neuronal cells. Cells were assigned to one of the four groups as follows: control group, leptin alone group, glutamate injury group, and leptin pretreatment group. Our results demonstrated that glutamate induced a decrease in superoxide dismutase, GSH (glutathione), and mitochondrial membrane potential and an increase in GSSG (oxidized glutathione), mitochondrial reactive oxygen species, and supplementation of leptin blocked the toxic effect of glutamate on cell survival. The glutamate-induced cytotoxicity was associated with an increase in mitophagy and intracellular zinc ion levels. Furthermore, glutamate activated the mitophagy markers PINK1, Parkin, and the ratio of LC3-II/LC3-I, as well as increased the expression of zinc transporter 3 (ZnT3). Leptin corrected these glutamate-caused alterations. Finally, the mitophagy inhibitor, CsA, significantly reduced intracellular zinc ion content and ZnT3 expression. These results suggest that mitophagy-mediated zinc dyshomeostasis and mitochondrial activation contributed to glutamate-induced HT22 neuronal cell injury and that leptin treatment could counteract these detrimental effects, thus highlighting mitophagy-mediated zinc homeostasis via mitochondrial activation as a potential strategy to counteract neuroexcitotoxicity.

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Antioxidative and Antiapoptotic Effects of Delta-Opioid Peptide [D-Ala2, D-Leu5] Enkephalin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Cited by 15 publications

References 24 publications

Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression

Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression

Delta Opioid Peptide [d-Ala2, d-Leu5] Enkephalin (DADLE) Exerts a Cytoprotective Effect in Astrocytes Exposed to Oxygen-Glucose Deprivation by Inducing Autophagy

Leptin Maintained Zinc Homeostasis Against Glutamate-Induced Excitotoxicity by Preventing Mitophagy-Mediated Mitochondrial Activation in HT22 Hippocampal Neuronal Cells

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