title: 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.
abstract: 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.
authors.affiliation: Section of Endocrine Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Evenson
authors.forename: Jamie
authors.initials: J
authors.lastname: Mitchell
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Poylin
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: 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*
chemical_list: 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