Impaired Na+,K+-ATPase activity as a mechanism of reactive nitrogen species-induced cytotoxicity in guinea pig liver exposed to lipopolysaccharides.

Cimen B., Turkozkan N., Seven I., Unlu A., Karasu Ç.

Molecular and cellular biochemistry, cilt.259, sa.1-2, ss.53-7, 2004 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 259 Sayı: 1-2
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1023/b:mcbi.0000021344.64317.a2
  • Dergi Adı: Molecular and cellular biochemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.53-7
  • Anahtar Kelimeler: 3-nitrotyrosine, Na+,K+-ATPase, iNOS, liver, guinea pig, NITRIC-OXIDE SYNTHASE, PERFORMANCE LIQUID-CHROMATOGRAPHY, POLY(ADP-RIBOSE) SYNTHETASE, ELECTROCHEMICAL DETECTION, DIFFERENTIAL INDUCTION, ENDOTOXIC-SHOCK, CEREBRAL-CORTEX, MESSENGER-RNA, KUPFFER CELLS, PEROXYNITRITE
  • Gazi Üniversitesi Adresli: Evet

Özet

In animal models of endotoxin, the excess production of NO and the reactive nitrogen species (RNS), are potent oxidant and nitrating agents, lead to lipid peroxidation, apoptosis, tissue dysfunction and injury and inactivate enzymes in many cell types. Although liver functions are well known to deteriorate following bacterial infection, the underlying specific mechanism(s) remain a matter of considerable debate. Therefore, the aim of the present study was to determine the in vivo effect of bacterial lipopolysaccharides (LPS) on Na+, K+-ATPase activity of guinea pig liver, and to investigate the possible contribution of RNS by measuring of iNOS activity and 3-nitrotyrosine (nTyr) levels. Liver Na+, K+-ATPase activity were maximally inhibited 6 h after LPS injection (p < 0.001). nTyr was not detectable in liver of normal control animals, but was detected markedly in LPS exposed animals. LPS treatment significantly increased iNOS activity of liver (p < 0.001). The regression analysis revealed a very close correlation between Na+, K+-ATPase activity and nTyr levels of LPS treated animals (r = -0.863, p < 0.001). Na+, K+-ATPase activity were also negatively correlated with iNOS activity (r = -0.823, p < 0.003) in inflamed tissues. Our results have strongly suggested that bacterial LPS disturbs activity of membrane Na+, K+-ATPase that may be an important component leading to the pathological consequences such as hepatocyte cell loss and dysfunction in which the production of RNS are increased as in the case of LPS challenge.