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, Oʹ2-dibutyryl cAMP (dbcAMP) or N6monobutyryl 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 (CIcAMP) and 1 mM dbcAMP enhanced the mean secreted activity/cell three- and fivefold, respectively. Oʹ2-monobutyryl cAMP (Oʹz-mbcAMP) did not affect ECSOD synthesis. The enhancement in EC-SOD activity did not require activation of protein kinase A. ATP, TGF-ß, IFN-y, 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.