Mood-enhancing antidepressant St. John's wort inhibits the activation of human immunodeficiency virus gene expression by ultraviolet light.
Ultraviolet (UV) radiation is a potent activator of the human immunodeficiency virus (HIV) gene expression in a HeLa cell clone with stably integrated copies of the HIVcat reporter construct. Recently, we have shown that activation of p38 MAP kinase and NF-kappaB is necessary but not sufficient for triggering efficient HIV gene expression in response to UV. Here we demonstrate that St. John's wort is a potent inhibitor of the UV-induced activation of HIV gene expression in HeLa cells. Stably transfected HIVcat/HeLa cells were preincubated with different amounts (25-100 microl) of St. John's wort or gingko biloba extracts for 30 min, then irradiated with UV (30 J/m2). In contrast to ginkgo biloba, St. John's wort inhibited the UV-induced HIV gene expression in a dose-dependent manner. Furthermore, preincubation with St. John's wort (10, 20, and 30 microl) for 30 min before UV (30 J/m2) irradiation, PMA- and UV-induced NF-kappaB activation was completely blocked, whereas ginkgo biloba did not affect the PMA- and UV-induced NF-kappaB activation in HeLa cells. UV activation of p38 MAP kinase was not inhibited by St. John's wort or by ginkgo biloba. However, we found that p38 MAP kinase and JNK1 and -2 were activated by St. John's wort, but p44/42 MAP kinase was not activated by St. John's wort in HeLa cells. Hypericin an active ingredient in St. John's wort also inhibited the UV activation of HIV gene expression in HeLa cells. These results firmly confirm that St. John's wort is a potent inhibitor of the UV-induced activation of HIV gene expression in HeLa cells.
Taher
Mohiuddin M
MM
Department of Neurology and Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298, USA. mtaher@mail2.vcu.edu
Lammering
Guido M
GM
Hershey
Chad M
CM
Valerie
Kristoffer C
KC
D000873:Anthracenes; D000928:Antidepressive Agents / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D002701:Chloramphenicol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D020441:Ginkgo biloba / Q000378:metabolism; D006678:HIV / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D020902:Hypericum / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D000873:Anthracenes; D000928:Antidepressive Agents; D002087:Butyrates; D016328:NF-kappa B; D010569:Perylene; D002701:Chloramphenicol; C004965:hypericin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases