Effect of 1,2 - Dymethylhydrazine on Sphingomyelin Metabolism and Protein Kinase Activities in Rat Liver

ABSTRACT

A weekly administration of 1,2 -dimethylhidrazine (DMH) for 30, 60 and 90 days for stimulation of sphingomyelin metabolism was used in this study and the behaviour of protein kinase A and C has been investigated under these conditions. DMH—treatment caused two-fold increase of the membrane cholesterol and of the percent participation of phosphatidylserine compared to the control values. The other phospholipid species did not undergo any significant changes. The increased cholesterol level led to stimulation of sphingomyelin synthesis and inhibition of its hydrolysis. An activation of alkaline ceramidase was observed as well. The data on membrane-bound and cytosolic protein kinase C activities revealed 2.5-fold increase of the particular activity. This augmentation might be due to activation of the particular form of the enzyme or to the translocation of the cytosolic form to the membrane bilayer since a decrease of cytosolic activity after DMH—treatment was established. The detected enhancement of protein kinase A might be as a result of the increased accumulation of sphingosine due to the increased activation of alkaline ceramidase.

Keywords:

• Sphingomyelin synthesis
• sphingomyelinase
• ceramidase
• plasma membrane
• protein kinase A
• protein kinase C