Acupuncture Regulates the Unfolded Protein Response and Inhibits Apoptosis in a Rat Model of Heroin Relapse

2016 ◽  
Vol 34 (6) ◽  
pp. 441-448 ◽  
Author(s):  
Yang Zhang ◽  
Xing-Hui Cai ◽  
Rong-Jun Zhang ◽  
Xiao-Rong Hou ◽  
Xiao-Ge Song ◽  
...  
Keyword(s):  
Protein Expression ◽  
Unfolded Protein Response ◽  
Brain Damage ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Pcr Array ◽  
Expression Levels ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Object To explore the unfolded protein response (UPR) in the hippocampus of rats undergoing heroin relapse and the mechanisms underlying the acupuncture-mediated inhibition of brain damage caused by heroin relapse. Methods 60 Sprague-Dawley rats (30 females and 30 males) were randomly divided into four groups: Control group, Heroin group, Heroin+acupuncture group, and Heroin+methadone group (n=15 each). In the latter three groups, a model of heroin addiction was established by successive increments of intramuscular heroin injections for 8 days, according to the exposure (addiction)→detoxification method. A UPR RT2 Profiler PCR array was used to screen for differentially expressed genes in the hippocampus. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. The protein expression levels of the following three differentially expressed genes were detected by Western blot to validate the results of the PCR array: heat shock protein (HSP)70, HSP105, and valosin-containing protein (Vcp). Results The UPR RT2 Profiler PCR Array detection results indicated that acupuncture increased the expression levels of the molecular chaperones HSP70, HSP105, and Vcp. The degree of neuronal apoptosis in the hippocampus of rats in the Heroin+acupuncture and Heroin+methadone groups was significantly reduced compared with the untreated Heroin group (p<0.01). Protein expression of HSP70, HSP105, and Vcp in the Heroin+acupuncture and Heroin+methadone groups was significantly higher than the Heroin group (p<0.01). Conclusions The positive effects of acupuncture on brain damage caused by heroin may be closely related to up-regulation of HSP70, HSP105, and Vcp, and reduced apoptosis.

scholarly journals RiboTag-Seq Reveals the Activation of the Unfolded Protein Response in Striatal Microglia Induced by Ethanol Withdrawal

2020 ◽  
Author(s):  
Brett D. Dufour ◽  
Kevin R. Coffey ◽  
Atom J. Lesiak ◽  
Gwenn A. Garden ◽  
John F. Neumaier
Keyword(s):  
Gene Expression ◽  
Unfolded Protein Response ◽  
Alcohol Intoxication ◽  
Ethanol Withdrawal ◽  
Differentially Expressed ◽  
Cytokine Signaling ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
The Impact

Repeated cycles of alcohol intoxication and withdrawal both induce profound changes in gene expression that can contribute to the physiological and behavioral consequences of ethanol. Since neuroinflammation is an important consequence of these changes, we used a novel strategy to investigate the impact of repeated cycles of chronic intermittent ethanol vapor and withdrawal on the RNAs actively undergoing translation in striatal microglia. RiboTag was selectively expressed in the microglia of transgenic mice and was used to immunopurify the RNA “translatome” from striatal microglia, yielding a snapshot of RNA translation during alcohol intoxication and after 8 hours of withdrawal. We obtained highly enriched microglial RNAs and analyzed these in individual animals by deep sequencing. We found a dramatic shift in gene expression during acute intoxication compared to air-exposed controls, with increases in genes and pathways associated with cytokine signaling, indicating increased neuroinflammation and microglial activation. After 8 hours of ethanol withdrawal, many inflammatory pathways remained upregulated but phagocytotic and proapoptotic pathways were increased. Using an unbiased bioinformatic method, weighted gene coexpression network analysis, multiple differentially expressed gene modules were identified. One in particular was differentially expressed in ethanol intoxicated vs. withdrawing animals, and there was a strong correlation between the centrality of the genes to this gene network and their individual statistical significance in differential expression. The unfolded protein response was over-represented in this network after withdrawal. The induction of this pathway in microglia is important since this cellular stress response can either lead towards restoration of normal function or apoptosis.

The unfolded protein response affects neuronal cell cycle protein expression: Implications for Alzheimer's disease pathogenesis

2006 ◽  
Vol 41 (4) ◽  
pp. 380-386 ◽  
Author(s):  
Jeroen J.M. Hoozemans ◽  
Jens Stieler ◽  
Elise S. van Haastert ◽  
Robert Veerhuis ◽  
Annemieke J.M. Rozemuller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Protein Expression ◽  
Unfolded Protein Response ◽  
Neuronal Cell ◽  
Cell Cycle Protein ◽  
Disease Pathogenesis ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Loss of slc39a14 causes simultaneous manganese deficiency and hypersensitivity in zebrafish

2020 ◽  
Author(s):  
Karin Tuschl ◽  
Richard J White ◽  
Leonardo E Valdivia ◽  
Stephanie Niklaus ◽  
Isaac H Bianco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Manganese Deficiency ◽  
Loss Of Function ◽  
Unfolded Protein ◽  
Manganese Neurotoxicity ◽  
Manganese Uptake ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractMutations in SLC39A14, a manganese uptake transporter, lead to a neurodegenerative disorder characterised by accumulation of manganese in the brain and rapidly progressive dystonia-parkinsonism (Hypermanganesemia with Dystonia 2, HMNDYT2). Similar to the human phenotype, zebrafish slc39a14U801-/- mutants show prominent brain manganese accumulation and abnormal locomotor behaviour. In order to identify novel potential targets of manganese neurotoxicity, we performed transcriptome analysis of individual homozygous mutant and sibling slc39a14U801 zebrafish at five days post fertilisation unexposed and exposed to MnCl2. Anatomical gene enrichment analysis confirmed that differentially expressed genes map to the central nervous system and eye. Biological interpretation of differentially expressed genes suggests that calcium dyshomeostasis, activation of the unfolded protein response, oxidative stress, mitochondrial dysfunction, lysosomal disruption, apoptosis and autophagy, and interference with proteostasis are key events in manganese neurotoxicity. Differential expression of visual phototransduction genes also predicted visual dysfunction in mutant larvae which was confirmed by the absence of visual background adaptation and a diminished optokinetic reflex. Surprisingly, we found a group of differentially expressed genes in mutant larvae that normalised upon MnCl2 treatment suggesting that, in addition to neurotoxicity, manganese deficiency is present either subcellularly or in specific cells or tissues. This may have important implications for treatment as manganese chelation may aggravate neurological symptoms. Our analyses show that slc39a14U801-/- mutant zebrafish present a powerful model to study the cellular and molecular mechanisms underlying disrupted manganese homeostasis.Significance statementManganese neurotoxicity leading to progressive dystonia-parkinsonism is a characteristic feature of Hypermanganesemia with dystonia 2 (HMNDYT2) caused by mutations in SLC39A14, a manganese uptake transporter. Transcriptional profiling in slc39a14U801 loss-of-function zebrafish suggests that, in addition to manganese neurotoxicity, subcellular or cell type specific manganese deficiency contributes to the disease phenotype. Both manganese overload and deficiency appear to be associated with Ca2+ dyshomeostasis. We further demonstrate that activation of the unfolded protein response, oxidative stress, mitochondrial dysfunction, apoptosis and autophagy, and disrupted proteostasis are likely downstream events in manganese neurotoxicity. Our study shows that the zebrafish slc39a14U801 loss-of-function mutant is a powerful model to elucidate the mechanistic basis of diseases affected by manganese dyshomeostasis.

Oestrogen-driven changes in the bovine uterus are associated with activation of the unfolded protein response

2014 ◽  
Author(s):  
Mohammed A Alfattah ◽  
Paul Anthony McGettigan ◽  
John Arthur Browne ◽  
Khalid M Alkhodair ◽  
Katarzyna Pluta ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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