Inhibition of mitochondrial protein synthesis influences the glucocorticoid sensitivity of lymphoid cells.
Inhibition of mitochondrial protein synthesis impairs the formation of the 13 polypeptides encoded on the mitochondrial genome. These polypeptides are part of enzyme complexes involved in oxidative phosphorylation. Prolonged inhibition of mitochondrial protein synthesis thus reduces the oxidative phosphorylation capacity which ultimately results in impairment of energy-requiring processes. Via a different mechanism glucocorticoid hormones also decrease the oxidative phosphorylation capacity of, e.g., lymphoid cells. The present study shows that inhibition of mitochondrial protein synthesis influences glucocorticoid-induced responses of lymphoid cells in two opposing manners. (a) It is enhanced after induction in cells with a reduced oxidative phosphorylation capacity resulting from preceding inhibition of mitochondrial protein synthesis. This can be explained by the synergistic effects of glucocorticoids and prolonged inhibition of mitochondrial protein synthesis on energy-producing processes. (b) It is counteracted when mitochondrial protein synthesis is impaired during induction of the response. The latter observation suggests that mitochondrial protein synthesis is involved in the generation of glucocorticoid-induced effects on lymphoid cells.
Van den Bogert
C
C
Laboratory of Physiological Chemistry, State University Groningen, The Netherlands.
Dontje
B H
BH
Melis
T E
TE
van der Veen
C
C
Kroon
A M
AM
D000315:Adrenalectomy; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D004357:Drug Synergism; D004734:Energy Metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007942:Leukemia, Experimental / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000033:anatomy & histology; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D003907:Dexamethasone; D004318:Doxycycline