Expression Of Mitochondrial Uncoupling Protein 3 During Lipid Storage Myopathy

A lipid storage myopathy(LSM) is one in which abnormal amounts of lipid accumulate in muscle in a pattern which correlates with the oxidative capacity of muscle fibers.Bradley et al.[1]first described a young patient with a subacute proximal myopathy and excessive lipid accumulation in type 1 muscle fibres in 1969.These authors defined this new pathological condition as LSM. The accumulation of lipid represents the predominant pathological alteration. Normal human muscle fibers contain sparse lipid deposits[2].There has been intense interest in defining the functions of uncoupling protein 3(UCP3) during the thirteen years since the cloning of this uncoupling protein 1(UCP1) homologue.UCP3 is a member of the superfamily of mitochondrial anion transporters localized in the inner membrane of the mitochondria,which expressed predominantly in the skeletal muscle of rodents and humans[3].Based on its high degree of homology to UCP1, early studies examined a role for UCP3 in thermogenesis. However, evidence for such a function is lacking. Recent studies have focused on two respects:UCP3 exports fatty acid(FA) anions or lipid peroxide products from mitochondria matrix in situations where FA entry into the mitochondria may exceed theβ- oxidation capacity.This would prevent a deleterious intramitochondrial accumulation of FA or lipid peroxide products and promote the metabolism of FA;UCP3 mitigates reactive oxygen species(ROS)production and in this way prevent or ameliorate oxidative damage.LSM is a well characterized model in which FA supply exceeds mitochondriaβ-oxidation capacity.With this in mind, it was interesting to study UCP3 expression in LSM patients. In the present study we measured the level of expression of UCP3 protein,intramyocellular lipid,oxidative stress and pathological changes in the tissues from muscle biopsies of 10 patients with LSM.Objective:To observe the expression of uncoupling protein 3(UCP3) in tissues from muscle biopsies of patients with lipid storage myopathy(LSM) and explore the the relationship between UCP3 and LSM and the diagnostic and therapeutic value of UCP3 in LSM.Methods:This study had two groups:experiment group(ten patients with LSM);control group(patients with polymyositis,mitochondria myopathy and amyotrophic lateral sclerosis in 5 cases each and 10 normal subjects).All subjects were diagnosed by muscle biopsies with light microscopic and/or electronic microscopic examination.A signed informed consent was obtained in each subject.Open muscle biopsies of the bicipital or quadriceps muscles were performed on all subjects.We used Western blot to detect the expression of UCP3 protein,and used assay Kit to detect the level of malondialdehyde,catalase and superoxide dismutase in muscle biopsies.The muscle biopsies of the subjects were done with routine histological and histochemical staining. Light microscopic studies were performed.Results:(1)Long chain UCP3(UCP3L) protein expression was found to be dramatically decreased in LSM patients but not in polymyositis,mitochondria myopathy,amyotrophic lateral sclerosis patients and normal subjects.(2)The catalase and superoxide dismutase activity increased in LSM,polymyositis,mitochondria myopathy and amyotrophic lateral sclerosis patients but not in normal subjects.There was no change of malondialdehyde content in all subjects.(3)Light microscopic:cracks and vacuoles of muscular fibers were observed by Hematoxylin-eosin(HE) staining in LSM patients;Oil red O(ORO) staining reaction was enhanced in all LSM patients and 2 mitochondria myopathy patients ;Adenosine triphosphate(ATP)staining showed amphitypy muscle fibers were all involved in,especially type I muscle fibers in LSM patients;Modified Gomori trichrome(MGT) staining of aLL mitochondria myopathy and 4 LSM patients showed ragged red fibers(RRF).Conclusions:The downregulation of UCP3L protein expression in LSM has relation with the accumulation of muscle lipid.UCP3 is important potential target for treatment of LSM.LSM is easily be diagnosis as other disease such as mitochondria myopathy or neurogenic myopathy.Muscle biopsy may lead to misdiagnosis,if combine with UCP3L detect may improve the accuracy rate of diagnosis.