Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia

Sadayuki Hashioka, Youn Hee Han, Shunsuke Fujii, Takahiro Kato, Akira Monji, Hideo Utsumi, Makoto Sawada, Hiroshi Nakanishi, Shigenobu Kanba

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO-), the reaction product of superoxide ({radical dot}O2-) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both {radical dot}O2- and NO by lipopolysaccharide (LPS)/phorbol 12-myristate-13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of {radical dot}O2- adduct associated with LPS/PMA-activated microglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and {radical dot}O2-, and thus presumably prevent a subsequent formation of ONOO-. Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of microglial activation.

Original languageEnglish
Pages (from-to)499-506
Number of pages8
JournalNeurochemistry International
Volume50
Issue number3
DOIs
Publication statusPublished - Feb 1 2007

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Microglia
Phosphatidylcholines
Superoxides
Lipopolysaccharides
Phospholipids
Nitric Oxide
Acetates
Liposomes
Phosphatidylserines
phorbol-12-myristate
Peroxynitrous Acid
Electron Spin Resonance Spectroscopy
Phagocytes
Neurodegenerative Diseases

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia. / Hashioka, Sadayuki; Han, Youn Hee; Fujii, Shunsuke; Kato, Takahiro; Monji, Akira; Utsumi, Hideo; Sawada, Makoto; Nakanishi, Hiroshi; Kanba, Shigenobu.

In: Neurochemistry International, Vol. 50, No. 3, 01.02.2007, p. 499-506.

Research output: Contribution to journalArticle

Hashioka, Sadayuki ; Han, Youn Hee ; Fujii, Shunsuke ; Kato, Takahiro ; Monji, Akira ; Utsumi, Hideo ; Sawada, Makoto ; Nakanishi, Hiroshi ; Kanba, Shigenobu. / Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia. In: Neurochemistry International. 2007 ; Vol. 50, No. 3. pp. 499-506.
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