Oxidation of nuclear membrane cholesterol inhibits nucleoside triphosphatase activity

Bram Ramjiawan, Michael P. Czubryt, Hamid Massaeli, James S.C. Gilchrist, Grant N. Pierce

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8 Citations (Scopus)

Abstract

Oxygen derived free radicals can oxidize membrane cholesterol. We have previously shown that cholesterol in the nuclear membrane can modulate nuclear nucleoside triphosphatase (NTPase) activity. Nucleocytoplasmic transport of peptides and mRNA via the nuclear pore complex may be regulated by the NTPase. The purpose of the present study was to determine if oxidation of nuclear cholesterol could alter NTPase activity. Nuclear membrane cholesterol was oxidized in situ with cholesterol oxidase (to selectively oxidize cholesterol) and NTPase activity measured. HPLC analysis confirmed the formation of cholesterol oxides. The activity of the NTPase was strikingly inhibited by cholesterol oxidase treatment. The V(max) of the NTPase was significantly decreased after cholesterol oxidase treatment but the K(m) value was unchanged. The sensitivity of NTPase activity to varying cholesterol oxidase concentrations also suggested that cholesterol located in the inner leaflet of the nuclear membrane appeared to be more important in the modulation of NTPase activity than that in the cytoplasmic leaflet. Our results indicate that oxidation of nuclear membrane cholesterol inhibits NTPase activity. These results have implications for peptide and mRNA flux across the nuclear membrane during conditions where lipid oxidation may be expected.

Original languageEnglish
Pages (from-to)556-562
Number of pages7
JournalFree Radical Biology and Medicine
Volume23
Issue number4
DOIs
Publication statusPublished - 22 Jul 1997

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Keywords

  • Cholesterol
  • NTPase
  • Nuclear membrane
  • Oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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