Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation

Kim, Soo Jeong; Ryu, Min Jeong; Han, Jin-Tae; Jang, Yunseon; Kim, Jungim; Lee, Min Joung; Ryu, Ilhwan; Ju, Xianshu; Oh, Eungseok; Chung, Woosuk; Kweon, Gi Ryang; Heo, Jun Young

doi:10.1016/j.bbrc.2017.09.017

Cited by 19 publications

(17 citation statements)

References 22 publications

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“…Although the unique characteristics of the tissue are well preserved, the heterogeneous cell population and the lack of proliferation of the primary dopaminergic neuron are obstacles to the study of molecular mechanisms [18, 27–29]. We further validated the protective effect of CP in the SN4741 dopaminergic neuronal cell line, a previously used immature dopaminergic neuronal cell line that is easier to culture than primary cells and is suitable for mechanism studies [19–22]. To examine the toxicity of CP, we treated SN4741 cells with different concentrations of CP alone for 48 h and found no evidence for cytotoxicity at concentrations up to 80 μ g/ml ().…”

Section: Resultsmentioning

confidence: 99%

“…The dopaminergic neuronal progenitor cell line (SN4741) was cultured as described before [19–22]. SN4741 cells were grown in RF medium containing Dulbecco's modified Eagle's medium (DMEM, Welgene) supplemented with 10% fetal bovine serum (FBS, Thermo Fisher Scientific Inc.), 1% glucose (Amresco, Solon, OH, USA), 1% penicillin-streptomycin, and 2 mM L-glutamine (Invitrogen) at 33°C with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

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Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson’s Disease Model

Han

Kim

Ryu

et al. 2019

Oxidative Medicine and Cellular Longevity

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Paraquat (PQ), an herbicide considered an environmental contributor to the development of Parkinson’s disease (PD), induces dopaminergic neuronal loss through reactive oxygen species (ROS) production and oxidative stress by mitochondrial complex I. Most patients with PQ-induced PD are affected by chronic exposure and require a preventive strategy for modulation of disease progression. To identify drugs that are effective in preventing PD, we screened more than 1000 drugs that are currently used in clinics and in studies employing PQ-treated cells. Of these, chloramphenicol (CP) showed the most powerful inhibitory effect. Pretreatment with CP increased the viability of PQ-treated SN4741 dopaminergic neuronal cells and rat primary cultured dopaminergic neurons compared with control cells treated with PQ only. CP pretreatment also reduced PQ-induced ROS production, implying that mitochondrial complex I is a target of CP. This effect of CP reflected downregulation of the mitochondrial complex I subunit ND1 and diminished PQ recycling, a major mechanism of ROS production, and resulted in the prevention of cell loss. Notably, these effects of CP were not observed in rotenone-pretreated SN4741 cells and Rho-negative cells, in which mitochondrial function is defective. Consistent with these results, CP pretreatment of MPTP-treated PD model mice also ameliorated dopaminergic neuronal cell loss. Our findings indicate that the inhibition of mitochondrial complex I with CP protects dopaminergic neurons and may provide a strategy for preventing neurotoxin-induced PD.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson’s Disease Model

Han

Kim

Ryu

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…The decrease in number and activity of catecholaminergic neurons will inevitably lead to insufficient activation of the DVMN and then reduce the output of CAP, which denotes that the curbing effect on inflammation by CAP decreases. The inflammation of the central nervous system not only enhances the TH expression but also promote the apoptosis of catecholaminergic neurons [ 50 ]; severe apoptosis of catecholaminergic neurons in sepsis gives rise to the reduction of CAP output. In this study, the expression of TH in MVZ catecholaminergic neurons decreased significantly in the sham group and the sepsis groups, indicating that catecholaminergic neurons were sensitive to stress, even surgical stress can also cause their dysfunction; in sepsis, sharp downregulation of expression of TH may be related to its excessive apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Zhou

Zhao³

et al. 2020

Mediators of Inflammation

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Inflammatory storm is an important pathological mechanism of multiple organ dysfunction, and it is associated with most deaths in septic patients, deserving to be studied. Recent findings have confirmed that the Medullary Visceral Zone (MVZ) regulates inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP), but how sepsis affects the MVZ and leads to uncontrolled inflammation remain unclear. The current study reported that sepsis induced MVZ to inhibit CAP which underlies the inflammation storm. Our studies have shown that the rat models of sepsis prepared by cecal ligation and puncture had a higher inflammatory level, higher mortality, and higher Murine Sepsis Score. In septic rats, some indicators of heart rate variability (HRV) such as SDNN, HF band, RMSSD, SD1, and SD2 significantly reduced. In MVZ of septic rats, many cholinergic and catecholaminergic neurons showed apoptotic, with low expressions of tyrosine hydroxylase and choline acetyltransferase. The α7nAChR agonist GTS-21 can improve these pathologies, while the α7nAChR antagonist MLA is the opposite. Our study demonstrates for the first time that cholinergic and catecholaminergic neurons in MVZ went through significant apoptosis and inactiveness in sepsis, which contributes to the inhibition of CAP and acceleration of the inflammation storm in early sepsis. Intervening with CAP has a significant effect on the activity and apoptosis of MVZ neurons while altering systemic inflammation and immunity; in addition, for the first time, we confirmed that some indicators of HRV such as SDNN, HF band, RMSSD, SD1, and SD2 can reflect the activity of CAP, but the CAP interference had little effect on these indicators.

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“…Recently, it has been reported that instant activation of JNK phosphorylation following treatment of cells with the HMGB1 (high mobility group box 1) protein cause an increase in the expression of tyrosine hydroxylase. The imbalance of this reduces dopamine synthesis and induces PD [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

Bohush

Niewiadomska

Filipek

2018

IJMS

118

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Parkinson’s disease (PD) is a neurodegenerative disorder caused by insufficient dopamine production due to the loss of 50% to 70% of dopaminergic neurons. A shortage of dopamine, which is predominantly produced by the dopaminergic neurons within the substantia nigra, causes clinical symptoms such as reduction of muscle mass, impaired body balance, akinesia, bradykinesia, tremors, postural instability, etc. Lastly, this can lead to a total loss of physical movement and death. Since no cure for PD has been developed up to now, researchers using cell cultures and animal models focus their work on searching for potential therapeutic targets in order to develop effective treatments. In recent years, genetic studies have prominently advocated for the role of improper protein phosphorylation caused by a dysfunction in kinases and/or phosphatases as an important player in progression and pathogenesis of PD. Thus, in this review, we focus on the role of selected MAP kinases such as JNKs, ERK1/2, and p38 MAP kinases in PD pathology.

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Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation

Cited by 19 publications

References 22 publications

Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson’s Disease Model

Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin-Induced Parkinson’s Disease Model

Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

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