The gene expression and activity of calpains and the muscle wasting-associated ubiquitin ligases, atrogin-1 and MuRF1, are not altered in patients with primary hyperparathyroidism.
Hyperparathyroidism (HPT) can be associated with muscle atrophy and weakness. Muscle atrophy is typically caused by increased muscle protein breakdown. The influence of HPT on calpains and the ubiquitin-proteasome pathway, which are important regulators of muscle proteolysis, is not yet known. We examined the expression in skeletal muscle of mu- and m-calpain and the ubiquitin ligases, atrogin-1 and MuRF1, in patients with primary HPT. A biopsy was obtained from the sternohyoid muscle in patients undergoing surgery for primary HPT (n=8) and in normocalcemic control patients undergoing thyroid surgery (n=11). mRNA levels for atrogin-1, MuRF1 and the calcium-regulated proteases, mu- and m-calpain, were determined by real-time PCR. Calpain activity was measured using the calpain-specific substrate, BODIPY-FL-casein, and by zymography. Serum calcium was 11.4+/-0.46 and 9.5+/-0.10 mg/dl in HPT and control patients, respectively (p<0.01). The corresponding phosphate levels were 2.7+/-0.2 and 3.6+/-0.1 mg/dl (p<0.05). Parathyroid hormone serum concentration was 286+/-103 pg/ml (range, 77-946 pg/ml) in patients with HPT and was not measured in control patients. There were no significant differences in mRNA levels for atrogin-1, MuRF1, mu- or m-calpain and in calpain activity between HPT and control patients. The results suggest that the ubiquitin-proteasome and calpain systems are not activated in skeletal muscle in patients with primary HPT, at least not in patients with moderate hypercalcemia.
Evenson
Amy
A
Section of Endocrine Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Mitchell
Jamie
J
Wei
Wei
W
Poylin
Vitaliy
V
Parangi
Sareh
S
Hasselgren
Per-Olof
PO
D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood; D002154:Calpain / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism* / Q000601:surgery; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D009124:Muscle Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases; D002154:Calpain; D002118:Calcium