Nitric oxide-induced accumulation of lipofuscin-like materials is caused by inhibition of cathepsin S

Eriko Sugano, Hiroshi Tomita, Sei Ichi Ishiguro, Hitomi Isago, Makoto Tamai

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

To determine whether nitric oxide (NO) is involved in accumulation of lipofuscin-like material (LFM) in retinal pigment epithelial (RPE) cells and if this formation is related to NO-mediated modification of cathepsin S (cat S). RPE cell cultures were fed once every day with porcine photoreceptor outer segments (POS) in the presence of NO-donor [ S -nitroso- N -acetylpenicillamine (SNAP) or NOC18] for 2 weeks. LFM autofluorescence within the cells was measured by fluorophotometric flow cytometry (FACS). The activity of purified cat S was measured in the presence of NO-donor with or without dithiothreitol (DTT). The following results were observed. SNAP and NOC18 caused LFM accumulation in RPE cells in a dose-dependent manner, and this accumulation was reversed by the addition of NO-scavengers (hydroxycobalamin, carboxy-PTIO). Purified cat S activities were inhibited by NO-donors without DTT, but in the presence of DTT, NO-donors exhibited no inhibitory effect on its activity. Phagocytic challenge of RPE cells increased cat S activity, which was reduced by the addition of NO donors. These results indicated that cat S activity was inhibited by NO-donors and resulted in LFM accumulation in RPE cells. We conclude that NO-mediated inhibition of cat S was caused through protein modification of cat S and resulted in LFM accumulation.

Original languageEnglish
Pages (from-to)607-616
Number of pages10
JournalCurrent Eye Research
Volume31
Issue number7-8
DOIs
Publication statusPublished - 2006 Aug 1

Keywords

  • Cathepsin S
  • Lipofuscin (LF)
  • Nitric oxide (NO)
  • Phagocytosis
  • Retinal piment epithelium (RPE)

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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