[Activities of Akt pathway and their correlation with pathological changes in myotonic dystrophy].
OBJECTIVE
To investigate the expression of Akt pathway and their correlation with pathological changes in the skeletal muscle of myotonic dystrophy 1 (DM1) patients.


METHODS
We chose 7 DM1 patients who were confirmed through clinical, electrophysiological and pathological data as DM1 patients group, and 7 patients without muscle pathological change as control group. The age range of DM1 patients group was from 6 to 35 years and disease duration was from 1 to 20 years. The clinical spectrum included distal myotonia, muscle weakness and atrophy. The serum creatine kinase ranged from 271 to 1 325 U/L; Electromyography showed myopathic changes together with diffusive myotonic discharges. We performed muscle biopsies in all the patients and tested total Akt, phosphorelated Akt, phosphorelated p70s6k in skeletal muscle specimens. We compared the Akt pathway activity of DM1 patients group with that of the control group and analyzed their correlation with the ratio of muscular hypertrophy, internal nuclei and basophilic sarcoplasmic masses.


RESULTS
Skeletal muscle biopsies revealed muscular dystrophic changes accompanied by peripherally placed sarcoplasmic masses and numerous internal nuclei. Increased optical density (D) of Akt, p-Akt, p-p70s6k had been noted in DM1 patients as compared with the controls (Akt: t=4.110, P=0.006; p-Akt: t=4.408, P=0.004; p-p70s6k: t=4.113, P=0.005; p-Akt/Akt: t=4.055, P=0.002). A positive linear correlation was observed between Akt pathway activity and muscle hypertrophy proportion (Akt group: r=0.825, P=0.015; p-Akt group: r=0.914, P=0.004; p-p70s6k group: r=0.916, P=0.004). But, no correlation was observed between Akt pathway and sarcoplasmic masses or internal nuclei.


CONCLUSIONS
Akt signaling pathway activity increased diffusively in skeletal muscle of the DM1 patient. Such elevation might be the cause of pathological muscle hypertrophy.
Department of Neurology, Peking University First Hospital, Beijing 100034, China.
Xiang
X
Li
Wei
W
Zhang
He
H
Lv
Zhao-xia
ZX
Wang
Yun
Y
Yuan
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009223:Myotonic Dystrophy / Q000378:metabolism* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
D051057:Proto-Oncogene Proteins c-akt