Inhibition of protein synthesis by chromium(VI) differentially affects expression of urokinase and its receptor in human type II pneumocytes.
Exposure to chromium(VI) increases the incidence of cancer, respiratory distress, and pulmonary fibrosis. The latter is a pathological disorder characterized by decreased urokinase-type plasminogen activator (uPA) activity and fibrinolysis. In this study, treatment of alveolar type II cells (A549) with 1 to 5 microM chromium(VI) for 4 and 12 h decreased both the specific activity and the amount of uPA protein. Chromium reduced uPA protein levels by inhibiting protein synthesis and had no effect on uPA mRNA levels or the rate of uPA protein degradation. In contrast, both mRNA and protein levels for the uPA receptor (uPAR) were increased by treatment with concentrations of chromium(VI) that did not completely inhibit protein synthesis. The chromium-induced increase in uPAR resulted from increased message stability. These data indicate that chromium has differential effects on expression of the proteins in the pulmonary fibrinolytic cascade. The net loss of uPA activity may promote fibrosis following inhalation of chromium(VI).
Shumilla
J A
JA
Department of Chemistry, Dartmouth College, Hanover, New Hampshire, USA.
Barchowsky
A
A
D002478:Cells, Cultured; D002857:Chromium / Q000737:chemistry / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D004791:Enzyme Inhibitors; C524898:PLAUR protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D002857:Chromium; D014568:Urokinase-Type Plasminogen Activator; D007930:Leucine