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 e xtracellular superoxide dismutase (EC-SOD) was studied in rat C6 gliom a. EC-SOD is constitutively expressed but stimulation with cAMP analog ues still increased the EC-SOD transcription and the secreted SOD acti vity. 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 o n the concentration of the cAMP analogues and on the cultivation time. Twenty-four hours after addition of 0.5 mM N-6, O'2-dibutyryl cAMP (d bcAMP) or N-6-monobutyryl cAMP (N-6-mbcAMP) EC-SOD mRNA expression inc reased approximately twofold, while stimulation for 68 h with 0.5 mM N -6-mbcAMP or 1 mM 8-Chloro cAMP (ClcAMP) and 1 mM dbcAMP enhanced the mean secreted activity/cell three- and fivefold, respectively. O'2-mon obutyryl cAMP (O'2-mbcAMP) did not affect EC-SOD synthesis. The enhanc ement 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.