Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy

Liang, Yucheng; Zhou, Tianen; Chen, Ying; Lin, Danyu; Jing, Xin; Peng, Sheng; Zheng, Duo; Zeng, Zhifen; Lei, Ming; Wu, Xia; Huang, Kaixun; Yang, Liguo; Xiao, Shifu; Li, Jun; Tao, Enxiang

doi:10.1016/j.neuro.2017.09.015

Cited by 45 publications

(39 citation statements)

References 43 publications

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“…Moreover, the protective effect of rifampicin on mitochondrial function is suppressed after the addition of the autophagy inhibitor. These results convince us that rifampicin leads to a reduction in ROS production through a tendency towards mitophagy (31).…”

Section: Rifampicin and Autophagysupporting

confidence: 72%

“…Chloroquine treatment, an autophagy inhibitor, inhibits the effect of rifampicin pretreatment on rotenone-stimulated IL-1β and IL-6 secretion. This indicates that rifampicin inhibits inflammation by modulating autophagy (31). In recent studies, various effects of rotenone have been shown on autophagy depending on the different dosages used and the cellular systems analyzed.…”

Section: Rifampicin and Autophagymentioning

confidence: 97%

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The Effects of Rifampicin on Neuronal Survival

Yurtsever¹,

Emekli-Alturfan²

2020

Experimed

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Neurodegenerative diseases are characterized by the formation of insoluble aggregates of misfolded proteins in the central nervous system. The β-amyloid protein in Alzheimer's disease and α-synuclein formation in Parkinson's disease (PD) may be given as examples. In addition to α-synuclein accumulation in Parkinson's disease, mechanisms such as oxidative stress, dysfunction of mitochondria, inflammation response, and apoptosis are known to be involved in the disease process. Since the mechanisms underlying these diseases are partially known, the drugs developed are intended to slow the disease process rather than cure them. Rifampicin is an antibiotic commonly used in humans and known to easily penetrate into the brain after oral intake. Studies have shown that rifampicin suppresses mitochondrial oxidative stress, eliminates α-synuclein fibrils and inhibits inflammation in in vitro and in vivo disease models. In this study, we reviewed recent studies on the neuronal protection of rifampicin and the effects of rifampicin on the pathophysiological mechanisms of PD.

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Section: Rifampicin and Autophagysupporting

confidence: 72%

Section: Rifampicin and Autophagymentioning

confidence: 97%

The Effects of Rifampicin on Neuronal Survival

Yurtsever¹,

Emekli-Alturfan²

2020

Experimed

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“…damage to neuronal cells. In this context, it was shown that rotenone increased the release of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in the BV2 cells [44] and in rat's brain tissues [33,52,65,74]. Microglial activation was reported to play a central pillar in rotenone-induced neuroinflammation.…”

Section: Mechanisms Of Action Of Rotenonementioning

confidence: 99%

Rotenone: from modelling to implication in Parkinson’s disease

Radad

Al‐Shraim

Al-Emam

et al. 2019

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Rotenone ([2R-(2α,6aα,12aα)]-1,2,12,12a-tetrahydro-8,9-dimethoxy-2-(1-methylethenyl)-[1]benzopyran[3,4-b]furo [2,3-h][1]benzopyran-6(6aH)-one) is a naturally occurring compound derived from the roots and stems of Derris, Tephrosia, Lonchocarpus and Mundulea plant species. Since its discovery at the end of the 19 th century, rotenone has been widely used as a pesticide for controlling insects, ticks and lice, and as a piscicide for management of nuisance fish in lakes and reservoirs. In 2000, Betarbet et al. reproduced most of the behavioural, biochemical and pathological features of Parkinson's disease (PD) in rotenone-treated rats. Since that time, rotenone has received much attention as it would be one of the environmental neurotoxins implicated in etiopathogenesis of PD. Moreover, it represents a common experimental model to investigate the underlying mechanisms leading to PD and evaluate the new potential therapies for the disease. In the current general review, we aimed to address recent advances in the hazards of the environmental applications of rotenone and discuss the updates on the rotenone model of PD and whether it is implicated in the etiopathogenesis of the disease.

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“…The pathological hallmarks of PD can be reproduced by rotenone injection, both systemically and regionally [ 10 , 11 ]. Rotenone functions as a mitochondrial complex I inhibitor, which can easily cross the blood-brain barrier (BBB) to induce mitochondrial dysfunction, leading to oxidative stress, energy dysmetabolism and neuroinflammation [ 12 , 13 ]. In addition, rotenone can induce α-synuclein accumulation, as well as activation of astrocytes and microglia to mediate inflammatory responses [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Pyrroloquinoline Quinone Inhibits Rotenone-Induced Microglia Inflammation by Enhancing Autophagy

et al. 2020

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Neuroinflammation is a feature common to neurodegenerative diseases, such as Parkinson’s disease (PD), which might be responsive to therapeutic intervention. Rotenone has been widely used to establish PD models by inducing mitochondrial dysfunction and inflammation. Our previous studies have reported that pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, could prevent mitochondrial dysfunction in rotenone induced PD models by regulating mitochondrial functions. In the present study, we aimed to investigate the effect of PQQ on neuroinflammation and the mechanism involved. BV2 microglia cells were pre-treated with PQQ followed by rotenone incubation. The data showed that PQQ did not affect the cell viability of BV2 cells treated with rotenone, while the conditioned medium (CM) of BV2 cells pre-treated with PQQ significantly increased cell viability of SH-SY5Y cells. In rotenone-treated BV2 cells, PQQ dose-dependently decreased lactate dehydrogenase (LDH) release and suppressed the up-regulation of pro-inflammation factors, such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the cultured media, as well as nitric oxide (NO) release induced by rotenone. PQQ pretreatment also increased the ratio of LC3-II/LC3-I and expression of Atg5 in BV2 cells stimulated with rotenone. Additionally, the autophagosome observed by transmission electron microscopy (TEM) and co-localization of mitochondria with lysosomes indicated that mitophagy was induced by PQQ in rotenone-injured BV2 cells, and the PINK1/parkin mediated mitophagy pathway was regulated by PQQ. Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.

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Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy

Cited by 45 publications

References 43 publications

The Effects of Rifampicin on Neuronal Survival

The Effects of Rifampicin on Neuronal Survival

Rotenone: from modelling to implication in Parkinson’s disease

Pyrroloquinoline Quinone Inhibits Rotenone-Induced Microglia Inflammation by Enhancing Autophagy

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