Lack of effects of hydrocortisone pretreatment on zinc-induced changes in protein assemble.
Inhalational zinc intoxication may lead to the development of acute respiratory distress syndrome (ARDS). Pharmacological treatment of ARDS is based on glucocorticoids, while the efficiency of glucocorticoid treatment is discussed controversially. Glucocorticoid pretreatment of lung cell lines is known to cause disparate effects with regard to zinc susceptibility. Both substances are known to each interact with protein metabolism. In the present study, zinc effects were examined on hydrocortisone (HC)-pretreated lung cell lines by detection of content and synthesis of different proteins after two-dimensional (2D) gel electrophoresis. (1) In HC- pretreated fibroblast-like 11Lu and alveolar epithelial L2 cells, no zinc-mediated changes after silver staining of 2D gels were seen. Few differences occurred in HC-pretreated alveolar epithelial A549 cells that might be explained by the appearance of heat shock proteins (hsp) after zinc exposure. (2) In autoradiographs after 35S-Met incorporation only in 11Lu cells, small differences occurred after HC treatment as compared to controls without HC. (3) All cell lines tested demonstrated the same zinc-mediated changes in autoradiographs with a nearly complete loss of synthesized proteins and an appearance of a few new spots. These changes were reversible in all cell lines after washing out of external zinc. The new spots were transiently expressed for a few hours after zinc exposure. (4) The overall effect of HC pretreatment was rather unimpressive. The virtual lack of major effects does not support the hypothesis that a gross interaction between glucocorticoids and zinc at the cellular protein synthesis level would be an important mechanism of influence in zinc-induced lung injury.
Walther
U I
UI
Walther Straub Institut für Pharmakologie und Toxikologie, München, Germany.
Mückter
H
H
Fichtl
B
B
Forth
W
W
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D004347:Drug Interactions; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013462:Sulfur Radioisotopes; D013997:Time Factors; D015032:Zinc / Q000633:toxicity*
D013462:Sulfur Radioisotopes; D008715:Methionine; D007770:L-Lactate Dehydrogenase; D015032:Zinc; D006854:Hydrocortisone