Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C.
The mechanism by which pertussis toxin (Ptx) causes lung edema is not clear. We investigated the role of pulmonary manganese superoxide dismutase (MnSOD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated that intraperitoneal injection of Ptx at a concentration of 5 microg/100 g body weight caused a similar degree of lung edema in 2 d, as measured by lung wet weight/dry weight ratio, in heterozygous MnSOD gene (Sod2)-knockout mice (Sod2(+/-)) and in their wild-type littermates (Sod2(+/+)). The level of lung MnSOD activity in Sod2(+/-) mice was approximately half that of Sod2(+/-) mice. Ptx had no effect on levels of lung MnSOD messenger RNA, immunoreactive protein, or enzyme activity in either Sod2(+/+) or Sod2(+/-) mice. Ptx also had no effect on lung copper-zinc SOD, catalase, and glutathione peroxidase activities in these mice. On the other hand, Ptx caused the activation of lung PKC, for example, by translocation of a 72-kD PKC isoform from the cytosolic fraction to the membrane fraction. Pretreatment of mice with bisindolylmaleimide, a PKC inhibitor, prevented both the Ptx-induced activation of PKC and lung edema. These data suggest that Ptx-induced lung edema in mice is, at least in part, due to the activation of lung PKC.
Research, Medical, and Laboratory Services, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, New York 12208, USA. tsan.min-fu@albany.va.gov
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Tsan
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Cao
J E
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White
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Sacco
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Lee
D000818:Animals; D000975:Antioxidants; D001692:Biological Transport; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism*; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000201:enzymology / Q000209:etiology; D012333:RNA, Messenger / Q000032:analysis; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000975:Antioxidants; D007527:Isoenzymes; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D013482:Superoxide Dismutase; D037342:Pertussis Toxin; D011493:Protein Kinase C