Sodium butyrate stimulates PKC activation and induces differential expression of certain PKC isoforms during erythroid differentiation.
Sodium butyrate (NaB) is an differentiation inducer currently under clinical investigation as a potential therapy for the treatment of sickle cell disease and prostate cancer. Though the biologic effects of this agent is well documented, its mechanism of action remains largely known. The mechanisms by which it transduces its signal to the nucleus is the subject of intense investigation in our laboratory. In this report, we demonstrate that NaB stimulates PKC activation by 3-fold and induces differential expression of several PKC isoforms. Notably, it upregulates PKC epsilon and downregulates PKC beta during erythroid differentiation. These findings suggest that certain PKC isoforms may play important roles in the signal transduction mechanisms of this agent leading to regulation of erythroid proliferation and differentiation.
Rivero
J A
JA
Biochemistry Department, Meharry Medical College, Nashville, Tennessee 37208, USA.
Adunyah
S E
SE
D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000187:drug effects; D005319:Fetal Hemoglobin / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000378:metabolism*; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002087:Butyrates; D007527:Isoenzymes; D020148:Butyric Acid; D005319:Fetal Hemoglobin; C497255:PRKCE protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon