Anti-inflammatory effect of oleuropein on microglia through regulation of Drp1-dependent mitochondrial fission

Park, Junghyung; Min, Ju-Sik; Chae, Unbin; Lee, Joon Yeop; Song, Kyung‐Sik; Lee, Hyun‐Shik; Lee, Hong Jun; Lee, Sang-Rae; Lee, Dong‐Seok

doi:10.1016/j.jneuroim.2017.02.019

Cited by 49 publications

(31 citation statements)

References 40 publications

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“…Data obtained with cultured cells (BV-2 microglial cells) showed the capacity of OLE (1, 5, and 10 μM) to inhibit the production of pro-inflammatory cytokines via regulation of ERK, P38 (MAPKs) and NF-κB activation. This work has also demonstrated that OLE can affects the LPS-induced mitochondria fission acting by decreasing the number of fragmented and elongated mitochondria via dephosphorylation of the Drp1 ( Park et al, 2017 ).…”

Section: Ole and Ht And The Molecular Mechanisms Implicated In Theirmentioning

confidence: 71%

Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation

Hornedo-Ortega

Cerezo

Pablos

et al. 2018

Front. Cell. Neurosci.

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Neuroinflammation is a pathological feature of quite a number of Central Nervous System diseases such as Alzheimer and Parkinson’s disease among others. The hallmark of brain neuroinflammation is the activation of microglia, which are the immune resident cells in the brain and represents the first line of defense when injury or disease occur. Microglial activated cells can adopt different phenotypes to carry out its diverse functions. Thus, the shift into pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective phenotypes, depending of the brain environment, has totally changed the understanding of microglia in neurodegenerative disease. For this reason, novel therapeutic strategies which aim to modify the microglia polarization are being developed. Additionally, the understanding of how nutrition may influence the prevention and/or treatment of neurodegenerative diseases has grown greatly in recent years. The protective role of Mediterranean diet (MD) in preventing neurodegenerative diseases has been reported in a number of studies. The Mediterranean dietary pattern includes as distinctive features the moderate intake of red wine and extra virgin olive oil, both of them rich in polyphenolic compounds, such as resveratrol, oleuropein and hydroxytyrosol and their derivatives, which have demonstrated anti-inflammatory effects on microglia on in vitro studies. This review summarizes our understanding of the role of dietary phenolic compounds characteristic of the MD in mitigating microglia-mediated neuroinflammation, including explanation regarding their bioavailability, metabolism and blood–brain barrier.

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Section: Ole and Ht And The Molecular Mechanisms Implicated In Theirmentioning

confidence: 71%

Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation

Hornedo-Ortega

Cerezo

Pablos

et al. 2018

Front. Cell. Neurosci.

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“…Lipopolysaccharide (LPS), a surface glycolipid of Gram-negative bacteria and an inflammatory endotoxin, has been found to stimulate mitochondrial fission, mitochondria- and NOX-derived superoxide production in immortalized microglial cell line [ 220 ]. As a regulated event, the observed ROS formation occurred downstream of the change in mitochondrial morphology since the effects were abolished by treatment with the antioxidant oleuropein, a secoiridoid glycoside abundant in olive leaf, which inhibited Drp1 Ser637 dephosphorylation as well as LPS-induced inflammation.…”

Section: Modulation Of Reactive Oxygen Species By Mitochondrial Dymentioning

confidence: 99%

Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

2018

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Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate redox signaling or, in excess, cause cell injury and even cell death. Recent evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS generation depending on the physiological status of the cell. Yet, the mechanism by which changes in mitochondrial shape modulate mitochondrial function and redox homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced ROS formation, which, in turn, may deteriorate mitochondrial health and further exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review the latest findings on the intricate relationship between mitochondrial dynamics and ROS production, focusing mainly on its role in malignant disease.

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“…Drp1-mediated mitochondrial ssion has been associated to enhanced activation of both p38 and NF-κβ, both mediators of signalling cascades leading to the expression of pro-in ammatory genes, in a paradigm of diabetic nephropathy [41]. Moreover, blocking Drp1-dephosphorylation with oleuropein reduced the production of pro-in ammatory factors in microglia as well [42]. In contrast, blockage of mitochondrial ssion with Mdivi-1 did not avoid the microglial metabolism switch to glycolysis upon LPS + IFN-γ exposure, nor did it provoke any effect in the control cells.…”

Section: Discussionmentioning

confidence: 99%

Role of mitochondrial dynamics in microglial activation and metabolic switch

Montilla

Ruiz

Matute

et al. 2020

Preprint

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Background Microglia are the endogenous immune cells of the central nervous system (CNS) and act as sensors of injury in the brain, favouring its homeostasis. Their activation and polarization towards a pro-inflammatory phenotype are associated to injury and disease. These processes are linked to a metabolic reprogramming of the cells, characterized by high rates of glycolytic function and suppressed levels of oxidative phosphorylation. This metabolic switch can be reproduced in vitro by stimulation with lipopolysaccharide (LPS) plus Interferon-γ (IFNγ). In an attempt to understand the mechanisms regulating mitochondrial respiration abolishment, we examined potential alterations in mitochondrial features during the metabolic switch. In addition, we studied the possible implication of mitochondrial dynamics in the metabolic switch using the mitochondrial division inhibitor-1 (Mdivi-1), which blocks Drp1-dependent mitochondrial fission. Methods Cultured microglia was treated with LPS + IFNγ to reproduce the metabolic switch under pro-inflammatory stimuli in the absence or in the presence of Mdivi-1 to block mitochondrial fission. Mitochondrial membrane potential and mitochondrial calcium were measured with living cell imaging, and microglial polarization was assessed by immunofluorescence and qRT-PCR. The metabolic profile of the cells was measured using the Seahorse XFe96 Extracellular Flux Analyzer. Results Under conditions of mitochondrial respiration abolishment, microglia did not show any change in mitochondria morphology, nor in mitochondrial membrane potential, indicative of a limited impact in its viability. We provided evidence that reverse operation of F0F1-ATP synthase contributes to mitochondrial membrane potential. On the other hand. mitochondrial fission blockage significantly reduced the expression of pro-inflammatory markers in LPS + IFNγ-treated microglia, such as the inducible nitric oxide synthase (iNOS). However, this inhibition did not lead to a recovery of the oxidative phosphorylation ablation by LPS + IFNγ or to a microglia repolarization. Conclusions Altogether, these results suggest that Drp1-dependent mitochondrial fission, although potentially involved in microglial activation, does not play an essential role in metabolic reprogramming and repolarization of microglia.

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Anti-inflammatory effect of oleuropein on microglia through regulation of Drp1-dependent mitochondrial fission

Cited by 49 publications

References 40 publications

Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation

Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation

Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression

Role of mitochondrial dynamics in microglial activation and metabolic switch

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