Involvement of C/EBPβ-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis

Huang, Enping; Huang, Hongyan; Guan, Tianshan; Liu, Chao; Qu, Dong; Xu, Yilin; Jiao, Yang; Liang, Yan; Xiong, Yahui; Liang, Ting; Wang, Qi; Chen, Ling

doi:10.1016/j.toxlet.2019.05.003

Cited by 31 publications

(12 citation statements)

References 62 publications

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“…This commonality suggests a shared pathological pathway (Jellinger, 2009;Martí et al, 2003) within synucleinopathies and other types of neurodegeneration. aSyn is a 140 amino acid long cytosolic protein that is proposed to be involved in numerous cellular functions with the detailed mechanisms still subject to debate (Bellani et al, 2010;Burré et al, 2010;Emamzadeh, 2016;Fusco et al, 2016;Huang et al, 2019;Villar-Piqué et al, 2016). The protein is highly dynamic and acts like a protein-chameleon, as it can adopt different conformations in different environments and purposes (Munishkina et al, 2003;Uversky, 2003).…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM structure of alpha-synuclein fibrils amplified by PMCA from PD and MSA patient brains

Burger

Fenyi

Bousset

et al. 2021

Preprint

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Synucleinopathies are neurodegenerative diseases related to the aggregation of the protein alpha-synuclein (aSyn). Among these diseases, Parkinson’s disease (PD) and multiple system atrophy (MSA) are most prevalent. aSyn can readily form different fibrillar polymorphs, if exposed to an air-water interface or by templating with pre-existing fibrils. We here report the structures of three fibrillar polymorphs that were obtained after seeding monomeric aSyn with PD and MSA patients brain homogenates using protein misfolding cyclic amplification (PMCA). Seeding with a control brain homogenate did not produce fibrils, and seeding with other in vitro generated fibrillar polymorphs as a control faithfully produced polymorphs of a different type. The here determined fibril structures from PD and MSA brain tissue represent new folds, which partly resemble that of previously reported in vitro generated fibrils from Y39 phosphorylated aSyn protein. The relevance of these fibrils for synucleinopathies in humans remains to be further investigated.Impact StatementNeurodegenerative diseases such as Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are suspected to be causatively related to the prion-like propagation of aggregates of the protein alpha-synuclein (aSyn). The fibril structures reported here were obtained after seeding from diseased human brain homogenate and differ from all previously published aSyn fibril arrangements. In case these fibrils would turn out to be the long sought causative agents of these diseases, their structures might lead to the development of therapeutic strategies to modify these diseases and to a better understanding of the mechanistic processes that lead to neurodegeneration and spreading of the diseases.

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Section: Introductionmentioning

confidence: 99%

Cryo-EM structure of alpha-synuclein fibrils amplified by PMCA from PD and MSA patient brains

Burger

Fenyi

Bousset

et al. 2021

Preprint

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“…Many studies indicated that the death of striatal neurons occurred by apoptosis and autophagy after METH exposure (Zhu et al, 2006). For example, C/EBPβ was involved in METH-induced DDIT4-mediated neuronal autophagy and Trib3-mediated neuronal apoptosis (Huang et al, 2019). Xu et al suggested that nuclear protein 1 (Nupr1/com1/p8) was involved in neuronal apoptosis and autophagy caused by high doses of METH through the endoplasmic reticulum (ER) stress signalling pathway (Xu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Role of HSP90α in Methamphetamine/Hyperthermia-Induced Necroptosis in Rat Striatal Neurons

Liao

Yan

et al. 2021

Front. Pharmacol.

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Methamphetamine (METH) is one of the most widely abused synthetic drugs in the world. The users generally present hyperthermia (HT) and psychiatric symptoms. However, the mechanisms involved in METH/HT-induced neurotoxicity remain elusive. Here, we investigated the role of heat shock protein 90 alpha (HSP90α) in METH/HT (39.5°C)-induced necroptosis in rat striatal neurons and an in vivo rat model. METH treatment increased core body temperature and up-regulated LDH activity and the molecular expression of canonical necroptotic factors in the striatum of rats. METH and HT can induce necroptosis in primary cultures of striatal neurons. The expression of HSP90α increased following METH/HT injuries. The specific inhibitor of HSP90α, geldanamycin (GA), and HSP90α shRNA attenuated the METH/HT-induced upregulation of receptor-interacting protein 3 (RIP3), phosphorylated RIP3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL. The inhibition of HSP90α protected the primary cultures of striatal neurons from METH/HT-induced necroptosis. In conclusion, HSP90α plays an important role in METH/HT-induced neuronal necroptosis and the HSP90α-RIP3 pathway is a promising therapeutic target for METH/HT-induced neurotoxicity in the striatum.

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“…C/EBPs act as dimers to bind to DNA in a sequence-specific manner to regulate transcription of the target genes [5][6][7]. Increasing evidence shows that C/EBPs play important roles in cell growth, differentiation, apoptosis, inflammation, aging, and neuronal autophagy [8][9][10][11][12][13].Emerging evidence has also implicated the crucial regulatory roles of C/EBPb in a few types of cancer, including breast cancer, pancreatic cancer, sarcoma, Abbreviations C/EBPb, CCAAT/enhancer-binding protein beta; TNBC, triple-negative breast cancer.…”

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confidence: 99%

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confidence: 99%

C/EBPβ regulates the JAK/STAT signaling pathway in triple‐negative breast cancer

et al. 2021

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C/EBPβ is a member of the CCAAT/enhancer-binding protein (C/EBP) family, which consists of a number of b-ZIP transcription factors. Although C/EBPβ has been implicated in the development of certain cancers, including breast cancer, it remains unknown whether dysregulation of C/EBPβ in breast cancer is subtype-specific. Moreover, the underlying mechanisms by which C/EBPβ regulates breast cancer carcinogenesis are not fully understood. Here, we present evidence that C/EBPβ is specifically overexpressed in human TNBC samples, but not in non-TNBC samples. C/EBPβ depletion dramatically suppressed TNBC cell growth, migration, invasion, and colony formation ability. A subsequent mechanistic study revealed that the JAK/STAT signaling pathway was upregulated in C/EBPβ_high TNBC samples compared to C/EBPβ_low TNBC samples. C/EBPβ ChIP-seq and QPCR was performed to demonstrate that C/EBPβ directly binds to and regulates JAK/STAT signaling pathway genes in TNBC. Taken together, our data indicate the oncogenic role of C/EBPβ in human TNBC and reveal a novel mechanism by which C/EBPβ promotes TNBC carcinogenesis.

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Involvement of C/EBPβ-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis

Cited by 31 publications

References 62 publications

Cryo-EM structure of alpha-synuclein fibrils amplified by PMCA from PD and MSA patient brains

Cryo-EM structure of alpha-synuclein fibrils amplified by PMCA from PD and MSA patient brains

The Role of HSP90α in Methamphetamine/Hyperthermia-Induced Necroptosis in Rat Striatal Neurons

C/EBPβ regulates the JAK/STAT signaling pathway in triple‐negative breast cancer

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