LIGHT-DEPENDENT INHIBITION OF PROTEIN-KINASE-C AND SUPEROXIDE GENERATION OF NEUTROPHILS BY HYPERICIN, AN ANTIRETROVIRAL AGENT

Hypericin, a photosensitizing plant pigment, has antiretroviral activi ty. When exposed to light, the inhibition of Friend leukemia virus (FL V)-induced splenomegaly by hypericin was increased. The ID50 was decre ased to less than 2.5 mu g/mouse by exposure to tungsten light (29 X 1 0(-3) W/cm(2) for 3 min). This pigment inhibited phorbol 12-myristate 13-acetate (PMA)-activated protein kinase C of rat brain in a light- a nd concentration-dependent manner. The ID50 of hypericin and the light intensity for inhibition of PKC were 0.1 mu M under a constant light of 29 X 10(-3) W/cm(2) for 3 min and 5 X 10(-3) W/cm(2) in the presenc e of 1 mu M hypericin for 3 min, respectively. The PMA-induced respira tory burst of neutrophils was inhibited in the light but stimulated in the dark by hypericin. The ID50 for inhibition of the respiratory bur st was similar to that for inhibition of PKC. These results suggest th at hypericin might inhibited PKC-mediated processes of intact cells, i ncluding PMA-induced superoxide generation of neutrophils by some ligh t-dependent mechanism, and that this mechanism might underlie its ligh t-dependent inhibition of FLV infection. (C) 1995 Academic Press, Inc.