Light-dependent inhibition of protein kinase C and superoxide generation of neutrophils by hypericin, an antiretroviral agent.
Hypericin, a photosensitizing plant pigment, has antiretroviral activity. When exposed to light, the inhibition of Friend leukemia virus (FLV)-induced splenomegaly by hypericin was increased. The ID50 was decreased to less than 2.5 micrograms/mouse by exposure to tungsten light (29 x 10(-3) W/cm2 for 3 min). This pigment inhibited phorbol 12-myristate 13-acetate (PMA)-activated protein kinase C of rat brain in a light- and concentration-dependent manner. The ID50 of hypericin and the light intensity for inhibition of PKC were 0.1 microM under a constant light of 29 x 10(-3) W/cm2 for 3 min and 5 x 10(-3) W/cm2 in the presence of 1 microM hypericin for 3 min, respectively. The PMA-induced respiratory burst of neutrophils was inhibited in the light but stimulated in the dark by hypericin. The ID50 for inhibition of the respiratory burst was similar to that for inhibition of PKC. These results suggest that hypericin might inhibited PKC-mediated processes of intact cells, including PMA-induced superoxide generation of neutrophils by some light-dependent mechanism, and that this mechanism might underlie its light-dependent inhibition of FLV infection.
Utsumi
T
T
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Okuma
M
M
Utsumi
T
T
Kanno
T
T
Yasuda
T
T
Kobuchi
H
H
Horton
A A
AA
Utsumi
K
K
D000818:Animals; D000873:Anthracenes; D000998:Antiviral Agents / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D004307:Dose-Response Relationship, Radiation; D005622:Friend murine leukemia virus; D006168:Guinea Pigs; D008027:Light; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000528:radiation effects; D012192:Retroviridae Infections; D013163:Splenomegaly; D013481:Superoxides / Q000378:metabolism; D014412:Tumor Virus Infections
D000873:Anthracenes; D000998:Antiviral Agents; D017319:Photosensitizing Agents; D013481:Superoxides; D010569:Perylene; C004965:hypericin; D011493:Protein Kinase C