Cyclic AMP-induced differentiation increases the synthesis of extracellular superoxide dismutase in rat C6 glioma.
The effect of membrane permeable cAMP analogues on the expression of extracellular superoxide dismutase (EC-SOD) was studied in rat C6 glioma. EC-SOD is constitutively expressed but stimulation with cAMP analogues still increased the EC-SOD transcription and the secreted SOD activity. The potency to enhance EC-SOD expression is correlated with the ability of the cAMP analogue to induce cAMP-dependent differentiation in C6. The increase in EC-SOD mRNA and in secreted activity depended on the concentration of the cAMP analogues and on the cultivation time. Twenty-four hours after addition of 0.5 mM N6, O'2-dibutyryl cAMP (dbcAMP) or N6-monobutyryl cAMP (N6-mbcAMP) EC-SOD mRNA expression increased approximately twofold, while stimulation for 68 h with 0.5 mM N6-mbcAMP or 1 mM 8-Chloro cAMP (ClcAMP) and 1 mM dbcAMP enhanced the mean secreted activity/cell three- and fivefold, respectively. O'2-monobutyryl cAMP (O'2-mbcAMP) did not affect EC-SOD synthesis. The enhancement in EC-SOD activity did not require activation of protein kinase A. ATP, TGF-beta, IFN-gamma, and LPS did not affect EC-SOD synthesis. The presented data point to a cAMP-dependent pathway for the enhanced expression of EC-SOD by glial cells in brain.
Nicolaï
S
S
Departement Biochemie, Universitaire Instelling Antwerpen, Belgium.
Willems
J
J
Zwijsen
A
A
Van Mechelen
E
E
Slegers
H
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005910:Glioma; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013449:Sulfonamides; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*
D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D007546:Isoquinolines; D012333:RNA, Messenger; D013449:Sulfonamides; C002373:monobutyryl cyclic AMP; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; C044258:8-chloro-cyclic adenosine monophosphate; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide