scholarly journals Brucella induces unfolded protein response and inflammatory response via GntR in alveolar macrophages

Oncotarget ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 5184-5196 ◽  
Author(s):  
Dong Zhou ◽  
Fei-Jie Zhi ◽  
Mao-Zhen Qi ◽  
Fu-Rong Bai ◽  
Guangdong Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Unfolded Protein Response ◽  
Alveolar Macrophages ◽  
Unfolded Protein ◽  
Protein Response

scholarly journals Induction of gut proteasome activity in hemorrhagic shock and its recovery by treatment with diphenyldihaloketones CLEFMA and EF24

2018 ◽  
Vol 315 (2) ◽  
pp. G318-G327 ◽  
Author(s):  
Geeta Rao ◽  
Hailey Houson ◽  
Gregory Nkepang ◽  
Hooman Yari ◽  
Chengwen Teng ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Hemorrhagic Shock ◽  
Unfolded Protein Response ◽  
Systemic Inflammatory Response ◽  
Proteasome Activity ◽  
26S Proteasome ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Unfolded Protein ◽  
Protein Response

Multiorgan failure in hemorrhagic shock is triggered by gut barrier dysfunction and consequent systemic infiltration of proinflammatory factors. Our previous study has shown that diphenyldihaloketone drugs 4-[3,5-bis[(2-chlorophenyl)methylene]-4-oxo-1-piperidinyl]-4-oxo-2-butenoic acid (CLEFMA) and 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone (EF24) restore gut barrier dysfunction and reduce systemic inflammatory response in hemorrhagic shock. We investigated the effect of hemorrhagic shock on proteasome activity of intestinal epithelium and how CLEFMA and EF24 treatments modulate proteasome function in hemorrhagic shock. CLEFMA or EF24 (0.4 mg/kg) were given 1 h after withdrawing 50% of blood from Sprague-Dawley rats; no other resuscitation was provided. After another 5 h of compensation, small gut was collected to process tissue for proteasome activity, immunoblotting, and mRNA levels of genes responsible for unfolded-protein response (XBP1, ATF4, glucose-regulated protein of 78/95 kDa, and growth arrest and DNA damage inducible genes 153/34), polyubiquitin B and C, and immunoproteasome subunits β type-8 and -10 and proteasome activator subunit 1. We found that hemorrhagic shock induced proteasome activity in gut tissue and reduced the amounts of ubiquitinated proteins displayed on antiubiquitin immunoblots. However, simultaneous induction of unfolded-protein response or immunoproteasome genes was not observed. CLEFMA and EF24 treatments abolished the hemorrhagic shock-induced increase in proteasome activity. Further investigations revealed that the induction of proteasome in hemorrhagic shock is associated with disassembly of 26S proteasome; CLEFMA and EF24 prevented this disassembly. Consistent with these data, CLEFMA and EF24 reduced hemorrhagic shock-induced degradation of 20S substrate ornithine decarboxylase in gut tissue. These results suggest that activated proteasome plays an important role in ischemic gut pathophysiology, and it can be a druggable target in shock-induced gut dysfunction. NEW & NOTEWORTHY Ischemic injury to the gut is a trigger for the systemic inflammatory response and multiple organ failure in trauma and hemorrhagic shock. We show for the first time that hemorrhagic shock induces the gut proteasome activity by engendering 26S proteasome disassembly. Diphenyldihaloketones 4-[3,5-bis[(2-chlorophenyl)methylene]-4-oxo-1-piperidinyl]-4-oxo-2-butenoic acid and 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone treatment prevented the 26S disassembly. Understanding the role of proteasome in shock-associated gut injury will assist in the development of therapeutic means to address it.

Unfolded protein response pathway, IRE1[alpha]-XBP1 is altered during adipogenesis in obese human adipocytes

2013 ◽  
pp. 1-1
Author(s):  
Philip Voyias ◽  
Ciara McCarthy ◽  
Adaikala Antonysunil ◽  
Warunee Kumsaiyai ◽  
Alison Harte ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Human Adipocytes ◽  
Unfolded Protein ◽  
Obese Human ◽  
Protein Response

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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