Protease inhibitors modulate apoptosis in mesangial cells derived from a mouse model of HIVAN11See Editorial by Foster, p. 1105.

Protease inhibitors modulate apoptosis in mesangial cells derived from a mouse model of HIVAN.BackgroundOxidative stress as well as opiate addiction has been shown to play a role in the development of complications associated with human immunodeficiency virus (HIV) infection.MethodsWe studied the occurrence of apoptosis in mesangial cells derived from control (NTrMC) mice and mice transgenic for HIV-1 genes (HTrMC) under basal and morphine-stimulated states (MSS). We evaluated the effect of free radical scavengers and antioxidants on HTrMC apoptosis and production of superoxide under basal and MSS. In addition, we examined the effect of protease inhibitors (PI) on apoptosis of NTrMCs/HTrMCs as well as morphine-induced superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase activation.ResultsHTrMCs showed greater apoptosis when compared with NTrMCs. Morphine triggered (P < 0.001) apoptosis of both NTrMCs and HTrMCs. Both antioxidants and free radical scavengers inhibited apoptosis of NTrMCs and HTrMCs under both basal and MSS. Morphine stimulated the production of superoxide by NTrMCs as well as by HTrMCs. Nevertheless, HTrMCs produced a greater (P < 0.001) amount of superoxide when compared with NTrMCs both under basal and MSS. PIs such as saquinavir and Indinavir inhibited HTrMC apoptosis in a dose-dependent manner. Saquinavir also protected HTrMCs against the proapoptotic effect of morphine. Moreover, saquinavir inhibited the production of superoxide by HTrMCs under both basal and MSS. Saquinavir also attenuated the morphine-induced expression of SOD and NADPH oxidase (Gp91phox) by HTrMCs. Interestingly, hemin exacerbated morphine-triggered HTrMC apoptosis.ConclusionOxidative stress seems to play a role in the accelerated rate of HTrMC apoptosis both under basal and MSS. Saquinavir may be inhibiting HTrMC apoptosis by mitigating oxidative stress