scholarly journals The HIV Protease Inhibitor Nelfinavir Downregulates Akt Phosphorylation by Inhibiting Proteasomal Activity and Inducing the Unfolded Protein Response

Neoplasia ◽  
2007 ◽  
Vol 9 (4) ◽  
pp. 271-278 ◽  
Author(s):  
Anjali K. Gupta ◽  
Bin Li ◽  
George J. Cerniglia ◽  
Mona S. Ahmed ◽  
Stephen M. Hahn ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Unfolded Protein Response ◽  
Hiv Protease ◽  
Hiv Protease Inhibitor ◽  
Proteasomal Activity ◽  
Akt Phosphorylation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

HIV protease inhibitors activate the unfolded protein response and disrupt lipid metabolism in primary hepatocytes

2006 ◽  
Vol 291 (6) ◽  
pp. G1071-G1080 ◽  
Author(s):  
Huiping Zhou ◽  
Emily C. Gurley ◽  
Sirikalaya Jarujaron ◽  
Hong Ding ◽  
Youwen Fang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Unfolded Protein Response ◽  
Protease Inhibitors ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Mrna Levels ◽  
Primary Hepatocytes ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Treatment of human immunodeficiency virus (HIV)-infected patients with HIV protease inhibitors (PIs) has been associated with serious lipid disturbances. However, the incidence and degree of impaired lipid metabolism observed in the clinic vary considerably between individual HIV PIs. Our previous studies demonstrated that HIV PIs differ in their ability to increase the levels of transcriptionally active sterol regulatory element-binding proteins (SREBPs), activate the unfolded protein response (UPR), induce apoptosis, and promote foam cell formation in macrophages. In the present study, we examined the effects of three HIV PIs, including amprenavir, atazanavir, and ritonavir, on the UPR activation and the expression of key genes involved in lipid metabolism in primary rodent hepatocytes. Both atazanavir and ritonavir activated the UPR, induced apoptosis, and increased nuclear SREBP levels, but amprenavir had no significant effect at the same concentrations. In rat primary hepatocytes, cholesterol 7α-hydroxylase (CYP7A1) mRNA levels were significantly decreased by atazanavir (38%) and ritonavir (56%) but increased by amprenavir (90%); 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase mRNA levels were increased by amprenavir (23%) but not by ritonavir and atazanavir; low-density lipoprotein receptor mRNA was increased by atazanavir (20%) but not by amprenavir and ritonavir. Similar results were obtained in mouse primary hepatocytes. Atazanavir and ritonavir also decreased CYP7A1 protein levels and bile acid biosynthesis, while amprenavir had no significant effect. The current results may help provide a better understanding of the cellular mechanisms of HIV PI-induced dyslipidemia and also provide useful information to help predict clinical adverse effects in the development of new HIV PIs.

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
Sign in / Sign up

Export Citation Format

Share Document