Antisense oligonucleotides targeted against protein kinase c alpha inhibit proliferation of cultured avian myoblasts.

Abstract

Protein kinase C (PKC) has been implicated in the control of proliferation and differentiation of many cell types. There is evidence indicating that it plays a role in signal transduction mechanisms related to myogenesis, but little is known about the individual functions of PKC isoforms in muscle cell development. Data obtained in previous studies using cultured chick embryo skeletal muscle cells suggested that PKC alpha is linked to the regulation of myoblast proliferation. However, this causal relationship could not be definitively established as no experiments based on selective inhibition of this isoform were carried out. In the present work, specific inhibition of the expression of PKC alpha in cultured myoblasts by using antisense oligonucleotide technology resulted in a significant decrease of culture cell density and DNA synthesis, clearly showing that this isoenzyme is involved in signalling pathways which promote muscle cell proliferation.