Modulation of dexamethasone-induced thymocyte apoptosis by heat-shock protein 90-binding agents.
Heat-shock protein 90 (HSP90) is known to affect a variety of cellular activities. The present study showed that the HSP90-binding agents, geldanamycin, herbimycin A and radicicol, inhibited the murine thymocyte apoptosis induced by dexamethasone and was accompanied by the inhibition of the reduction of the mitochondrial transmembrane potential (delta psi m). HSP90-binding agents did not inhibit etoposide-induced apoptosis. The inhibition of dexamethasone-induced apoptosis was in part due to the interference of HSP90 with the glucocorticoid receptor, resulting in the inhibition of nuclear translocation of the receptor. The expression of inositol 1,4,5-triphosphate receptors, which were shown to be involved in dexamethasone-induced apoptosis, did not participate in the inhibition of apoptosis.
Ohta
Kazumasa
K
Department of Biochemistry, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.
Okoshi
Rintarou
R
Wakabayashi
Maiko
M
Sato
Yutaka
Y
Kizaki
Harutoshi
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016227:Benzoquinones; D015220:Calcium Channels; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047029:Lactams, Macrocyclic; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology; D018942:Macrolides; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects; D011809:Quinones / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D016227:Benzoquinones; D015220:Calcium Channels; D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; C025389:Itpr1 protein, mouse; C488910:Itpr1 protein, rat; D047029:Lactams, Macrocyclic; D007783:Lactones; D018942:Macrolides; D008562:Membrane Glycoproteins; D011809:Quinones; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D017828:Rifabutin; D005047:Etoposide; C020754:herbimycin; D003907:Dexamethasone; C035359:monorden; C001277:geldanamycin