Identification of proteasome gene regulation in a rat model for HIV protease inhibitor-induced hyperlipidemia

摘要: Patients treated with highly active antiretroviral therapy may develop metabolic side effects such as hyperlipidemia, insulin resistance, lipoatrophy and lactic acidosis. The pathophysiology of these abnormalities is unknown, although some, e.g., acidosis lipoatrophy, are more associated nucleoside use while protease inhibitors (PIs) have been shown to contribute hyperlipidemia resistance. Identifying new PIs that not dyslipidemia has hindered by the lack mechanistic information unavailability relevant animal models. In order understand molecular mechanism behind other inhibitors, a effective, faster screen for compounds this liability, we analyzed expression profiles from PI-treated animals. Previously, treatment rats ritonavir results in increases proteasomal subunit genes liver. We show increase similar bortezomib, proteasome inhibitor. addition, additional including atazanavir, which lower rates lipid elevations clinic when administered absence ritonavir. Our indicate strong correlation between induction elevations, allowed us rapid identifying novel do induce proteasome.