Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent

Toshifumi Nishiuchi, Takahiko Utsumi, Tomoko Kanno, Yoshiki Takehara, Hirotsugu Kobuchi, Tamotsu Yoshioka, Alan A. Horton, Tatsuji Yasuda, Kozo Utsumi

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9 Citations (Scopus)

Abstract

We previously reported that phorbol 12-myristate 13-acetate (PMA)-induced superoxide[formula]generation of neutrophils was inhibited by hypericin, a photosensitizing pigment found in St. Johnswort (herbHypericin triquetrifoliumTurra), via a mechanism involving protein kinase C (PKC). To obtain further insights into the mechanism of inhibition, the effects of hypericin on stimulation-dependent[formula]generation and related enzymes of neutrophils were investigated. Hypericin inhibited[formula]generation of neutrophils induced by PKC-dependent and -independent stimuli in a light- and concentration-dependent manner. Oxygen was required for the light-dependent inhibition by hypericin. NADPH oxidase activity in a cell-free system and TNF-α-induced tyrosyl phosphorylation of neutrophil proteins were also inhibited by hypericin in a concentration- and light-dependent manner. However, tyrosine kinase of p60src, an enzyme not bound to a membrane, was not inhibited either in the light or in the dark. Oxygen uptake of neutrophils by photosensitization with hypericin resulted in the formation of singlet oxygen (1O2), [formula], and hydroxyl radical (·OH) and enhanced lipid peroxidation. The formation of1O2was inhibited by azide, a quencher of1O2, but not by desferrioxamine (DSF), a ferric ion chelator. By contrast, both generation of ·OH and lipid peroxidation were inhibited by DSF but not by azide. Furthermore, PMA-induced[formula]generation inhibited by hypericin partially recovered in the presence of azide but not DSF. These results suggested that the light-dependent inhibition of[formula]generation by hypericin might be due to inhibition of tyrosine kinase, PKC, and NADPH oxidase via an oxygen-dependent mechanism, possibly through both Type I and II photosensitization mechanisms.

Original languageEnglish
Pages (from-to)335-342
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume323
Issue number2
DOIs
Publication statusPublished - Nov 10 1995
Externally publishedYes

Keywords

  • Antiretroviral pigment
  • Hypericin
  • NADPH oxidase
  • Neutrophil [formula]
  • Photosensitization
  • Protein kinase C
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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  • Cite this

    Nishiuchi, T., Utsumi, T., Kanno, T., Takehara, Y., Kobuchi, H., Yoshioka, T., Horton, A. A., Yasuda, T., & Utsumi, K. (1995). Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent. Archives of Biochemistry and Biophysics, 323(2), 335-342. https://doi.org/10.1006/abbi.1995.9956