Genomic and non-genomic effects of different glucocorticoids on mouse thymocyte apoptosis.
Glucocorticoids, widely used therapeutic agents for several pathologies, act upon diverse cells and tissues, including the lympho-haemopoietic system. Glucocorticoid-mediated apoptosis has been described as one of the mechanisms underlying their pharmacological and physiological effects. Glucocorticoids induce apoptosis in thymocytes through genomic and non-genomic signals. We tested thymocyte apoptosis rates as induced by a panel of glucocorticoids. Using four glucocorticoids that are widely adopted in clinical practice we compared their induction of thymocyte apoptosis and activation of non-genomic and genomic signals, including phosphatidylinositol-specific phospholipase C (PI-PLC), caspase-8, -9 and -3, and Glucocorticoid-Induced Leucine Zipper (GILZ). GILZ is a protein that is rapidly induced by glucocorticoids treatment and involved in apoptosis modulation. Results indicate different glucocorticoids have different apoptotic activity which is related to their ability to induce both genomic, evaluated as caspases activation and GILZ expression, and non-genomic effects, evaluated as PI-PLC phosphorylation.
Bruscoli
Stefano
S
Department of Clinical and Experimental Medicine, Section of Pharmacology, Perugia University Medical School, Via del Giochetto, 06122 Perugia, Italy.
Di Virgilio
Rosa
R
Donato
Valerio
V
Velardi
Enrico
E
Baldoni
Monia
M
Marchetti
Cristina
C
Migliorati
Graziella
G
Riccardi
Carlo
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis
C498608:Dsip1 protein, mouse; D005938:Glucocorticoids; D014157:Transcription Factors; D054801:Phosphoinositide Phospholipase C; D020169:Caspases; D043265:Phosphatidylinositol Diacylglycerol-Lyase