Myotonic dystrophy: decreased levels of myotonin protein kinase (Mt-PK) leads to apoptosis in muscle cells.
The pathogenesis of myotonic dystrophy (DM) and the function of the product of the DM gene, myotonin protein kinase (Mt-PK), and its relationship to the disease are uncertain. To gain insight into the function of Mt-PK we studied the effect of decreasing the levels of Mt-PK in cultured human myoblasts. Myoblasts were transfected with an anti-sense oligonucleotide (ODN) targeted to the translation initiation site of DM mRNA which resulted in about 76% reduction in the levels of Mt-PK protein. A large percentage (about 48 to 90%) of myoblasts transfected with this oligonucleotide (but only about 2 to 23% of myoblasts transfected with a control oligonucleotide) underwent apoptosis within 24 h. To further substantiate these results we delivered a specific antibody to Mt-PK into the myoblast cells using a lipid carrier to inhibit its function and show that this resulted in apoptosis in 57 to 72% of the cells within 24 h. These results suggest that decreased levels of Mt-PK may contribute to muscle pathology in DM by leading to apoptosis of muscle cells.
Bhagavati
S
S
Department of Neurology, State University of New York Health Sciences Center, Brooklyn 11203, USA.
Bhagwati
S
S
Leung
B
B
Shafiq
S A
SA
Ghatpande
A
A
D017209:Apoptosis; D001483:Base Sequence; D002478:Cells, Cultured; D006801:Humans; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009223:Myotonic Dystrophy / Q000201:enzymology* / Q000473:pathology*; D065636:Myotonin-Protein Kinase; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010442:Peptide Chain Initiation, Translational; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000032:analysis / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
C585517:DMPK protein, human; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases