Motexafin gadolinium (Gd-Tex) selectively induces apoptosis in HIV-1 infected CD4+ T helper cells.
Here, we show that motexafin gadolinium (Gd-Tex), a compound that promotes intracellular oxidative stress, selectively induces apoptosis in HIV-1-infected CD4(+) T cells in IL-2-stimulated cultures of peripheral blood mononuclear cells infected in vitro with HIV-1. This selective induction of apoptosis, which we detect by FACS analysis of intracellular HIV/p24 and concomitant surface and apoptosis marker expression, is abrogated by the glutathione precursor, N-acetyl-l-cysteine. Importantly, it occurs at Gd-Tex concentrations that are not cytotoxic to uninfected cells in the culture. These findings suggest that Gd-Tex may have therapeutic utility as an anti-HIV agent capable of selectively targeting and removing HIV-infected cells in an infected host.
Perez
Omar D
OD
Department of Microbiology and Immunology, The Baxter Laboratories of Genetic Pharmacology, Stanford University, Stanford, CA 94305-5175, USA.
Nolan
Garry P
GP
Magda
Darren
D
Miller
Richard A
RA
Herzenberg
Leonard A
LA
Herzenberg
Leonore A
LA
D000111:Acetylcysteine / Q000494:pharmacology; D017304:Annexin A5 / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D002469:Cell Separation; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015497:HIV-1 / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology*; D008956:Models, Chemical; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology*; D013997:Time Factors
D017304:Annexin A5; D000970:Antineoplastic Agents; D004396:Coloring Agents; D008665:Metalloporphyrins; C437683:motexafin gadolinium; D010100:Oxygen; D000111:Acetylcysteine