TDP-43 toxicity is mediated by the unfolded protein response-unrelated induction of C/EBP homologous protein expression

2011 ◽  
Vol 90 (3) ◽  
pp. 641-647 ◽  
Author(s):  
Hiroaki Suzuki ◽  
Masaaki Matsuoka
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 ◽  
...  

2015 ◽  
Vol 22 (3) ◽  
pp. C1-C4 ◽  
Author(s):  
Souren Mkrtchian

The maturation of secretory and membrane proteins in the endoplasmic reticulum (ER) is tightly regulated by the unfolded protein response (UPR), a signal transduction pathway maintaining ER protein folding homeostasis. However, certain ER states are incompatible with cell survival and therefore the UPR may choose to eliminate severely disrupted cells by apoptosis. This is accomplished primarily through the activation of the transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP). In the April 2015 issue of Endocrine-Related Cancer, researchers from the universities of South Carolina and Athens (Greece) suggested a novel mechanism of CHOP-mediated apoptosis connected with the suppression of a prominent cell cycle regulator with anti-apoptotic activity, p21. These findings and suggested clinical applications, such as potentiation of cancer chemotherapy and a novel therapeutic approach for type 2 diabetes, are discussed in the context of UPR.


2016 ◽  
Vol 34 (6) ◽  
pp. 441-448 ◽  
Author(s):  
Yang Zhang ◽  
Xing-Hui Cai ◽  
Rong-Jun Zhang ◽  
Xiao-Rong Hou ◽  
Xiao-Ge Song ◽  
...  

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.


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

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