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

Research output: Contribution to journalArticle

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

Fingerprint

Anti-Retroviral Agents
Superoxides
Neutrophils
Deferoxamine
Azides
Light
Protein Kinase C
Photosensitivity Disorders
NADPH Oxidase
Oxygen
Protein-Tyrosine Kinases
Lipid Peroxidation
Acetates
Hypericum
Lipids
Singlet Oxygen
Phosphorylation
Cell-Free System
hypericin
Enzymes

Keywords

  • antiretroviral pigment
  • hypericin
  • NADPH oxidase
  • neutrophil [formula]
  • photosensitization
  • protein kinase C
  • tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Inhibition of Neutrophil Superoxide Generation by Hypericin, an Antiretroviral Agent. / Nishiuchi, Toshifumi; Utsumi, Takahiko; Kanno, Tomoko; Takehara, Yoshiki; Kobuchi, Hirotsugu; Yoshioka, Tamotsu; Horton, Alan A.; Yasuda, Tatsuji; Utsumi, Kozo.

In: Archives of Biochemistry and Biophysics, Vol. 323, No. 2, 10.11.1995, p. 335-342.

Research output: Contribution to journalArticle

Nishiuchi, T, Utsumi, T, Kanno, T, Takehara, Y, Kobuchi, H, Yoshioka, T, Horton, AA, Yasuda, T & Utsumi, K 1995, 'Inhibition of Neutrophil Superoxide Generation by Hypericin, an Antiretroviral Agent', Archives of Biochemistry and Biophysics, vol. 323, no. 2, pp. 335-342. https://doi.org/10.1006/abbi.1995.9956
Nishiuchi, Toshifumi ; Utsumi, Takahiko ; Kanno, Tomoko ; Takehara, Yoshiki ; Kobuchi, Hirotsugu ; Yoshioka, Tamotsu ; Horton, Alan A. ; Yasuda, Tatsuji ; Utsumi, Kozo. / Inhibition of Neutrophil Superoxide Generation by Hypericin, an Antiretroviral Agent. In: Archives of Biochemistry and Biophysics. 1995 ; Vol. 323, No. 2. pp. 335-342.
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