UBIQUITIN LIGASES MURF1 AND MAFBX IN HUMAN MUSCLE ATROPHY

Abstract

Introduction: Pathological conditions, which determine human atrophy, are numerouses and heterogeneous.

Experimental studies prove that these different pathological conditions use common enzymatic pathways leading muscle atrophy. In every catabolic conditions where there is proteolyses’s increase, this one happens in association with up-regulation of two specific genes of skeletal muscle atrophy. These genes, MuRf1 (muscle ring finger-1) and MAFbx (muscle atrophy F-box), encode ubiquitin ligases. These ligases bind and mediate ubiquitination of myofibrillar proteins for subsequent degradation during muscle atrophy.

The aim of our study is to obtain a better understanding of human muscle physiopathology in atrophy by use of histochemistry and immunolocalisation of MuRF-1 and MAFbx.

Patients and Methods: 15 patients, amputated at third distal or proximal leg because of different acute or chronic pathology, were divided in two group. Group A: 12 elderly patients (mean age 72 years) amputated for vascular diseases (8) and complication of a diabetic foot (4). Group B: 3 young patients involved in car accident (mean age 25) amputated for limb’s acute arterial insufficiency. Gastrocnemius muscle biopsy specimens were obtained for all the patients, after that the informed consent was obtain, for histochemical (haematossilineosin), and immunohistochemical (anti- MuRf1, anti- MAFbx) analysis.

Results: Histochemistry: Group A: skeletal muscle showed a decrease in fiber size in cross-sectional area and fiber length with adipose tissue. Group B: light skeletal muscle structural alteration. Immuno-histochemistry: in group A, in muscular drawings, polyclonal antibodies direct against MuRf1 and MAFbx had stained muscle biopsy specimens. Muscle fiber cells showed MuRf1 and MAFbx subsarcolemmatic immunoreactivity and weakly immunoreactivity of the extracellular matrix. We noticed no positivity to anti- MuRf1 and anti- MAFbx less in sections from group B muscle biopsy specimens and in sections in which were present tissue muscle degeneration with replacement of adipose tissue.

Conclusion: The pathological results supported the concept that MuRf1 and MAFbx appeared to be regulatory peptide in cellular pathology that conduce to muscular atrophy. Our data support the hypothesis that different pathological conditions use common enzymatic pathways leading muscle atrophy.

The demonstration that the muscle-specific proteins MAFbx and MuRF1 are upregulated in multiple pathological conditions of skeletal muscle atrophy it is critical to continue studying the cellular pathways to discover promising targets for the development of effective new treatments for skeletal muscle disease.