Peroxidative stress selectively down-regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction

2001 ◽  
Vol 76 (6) ◽  
pp. 1916-1924 ◽  
Author(s):  
Wulf Paschen ◽  
Thorsten Mengesdorf ◽  
Sonja Althausen ◽  
Svenja Hotop
eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Martin Larhammar ◽  
Sarah Huntwork-Rodriguez ◽  
Zhiyu Jiang ◽  
Hilda Solanoy ◽  
Arundhati Sengupta Ghosh ◽  
...  

The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly understood. Here we show that PERK signaling is a component of the mouse MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK-activating insults ranging from nerve injury to neurotrophin deprivation result in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent upregulation of the Activating Transcription Factor 4 (ATF4). Disruption of PERK signaling delays neurodegeneration without reducing JNK signaling. Furthermore, DLK is both sufficient for PERK activation and necessary for engaging the ISR subsequent to JNK-mediated retrograde injury signaling. These findings identify DLK as a central regulator of not only JNK but also PERK stress signaling in neurons, with both pathways contributing to neurodegeneration.


2020 ◽  
Author(s):  
Jui-Heng Tseng ◽  
Aditi Ajit ◽  
Zarin Tabassum ◽  
Niyati Patel ◽  
Xu Tian ◽  
...  

2006 ◽  
Vol 291 (3) ◽  
pp. H1411-H1420 ◽  
Author(s):  
Asim Azfer ◽  
Jianli Niu ◽  
Linda M. Rogers ◽  
Frances M. Adamski ◽  
Pappachan E. Kolattukudy

Endoplasmic reticulum (ER) stress has been found to be associated with neurodegenerative diseases and diabetes mellitus. Whether ER stress is involved in the development of heart disease is not known. Cardiac-specific expression of monocyte chemoattractant protein-1 (MCP-1) in mice causes the development of ischemic heart disease. Here we report that microarray analysis of gene expression changes in the heart of these transgenic mice revealed that a cluster of ER stress-related genes was transcriptionally activated in the heart during the development of ischemic heart disease. The gene array results were verified by quantitative real-time PCR that showed highly elevated transcript levels of genes involved in unfolded protein response such as ER and cytoplasmic chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER-associated degradation system such as ubiquitin. Immunoblot analysis confirmed the expression of chaperones, PDI, and ubiquitin. Immunohistochemical analyses showed that ER stress proteins were associated mainly with the degenerating cardiomyocytes. A novel ubiquitin fold modifier (Ufm1) that has not been previously associated with ER stress and not found to be induced under any condition was also found to be upregulated in the hearts of MCP mice (transgenic mice that express MCP-1 specifically in the heart). The present results strongly suggest that activation of ER stress response is involved in the development of ischemic heart disease in this murine model.


2000 ◽  
Vol 275 (35) ◽  
pp. 27013-27020
Author(s):  
Yan Wang ◽  
Jingshi Shen ◽  
Natalia Arenzana ◽  
Witoon Tirasophon ◽  
Randal J. Kaufman ◽  
...  

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