Altered structural and functional properties of myosins, from platelets of idiopathic scoliosis patients

Abstract

Platelets of patients with idiopathic scoliosis (IS) have been shown to have decreased capacity to aggregate and secrete in response to certain agonists. Similarities between the contractile protein system of platelets and muscle have made the platelets a popular model for muscle disease. We attempted to characterize the function and structure of myosin in platelets of IS patients. Blood was obtained from seven IS patients and seven matched non-scoliotic healthy controls. The mean Cobb angle measurement of the IS patients was 35.4 degrees with a mean Risser sign of 2.2. Washed platelets were isolated from the blood, and the contractile proteins from the membrane and the cytosol compartments were isolated and analyzed by two-dimensional peptide mapping. As previously reported (J Biol Chem 258:9290, 1983), peptide maps of normal platelets revealed that the heavy chain of myosin located in the platelet membrane lacks one major spot relative to the cytoplasmic myosin. In IS patients the cytoplasmic myosin lacks the same peptide that is missing in the membrane myosin of normal individuals. In addition, the ATPase specific activity of the cytoplasmic myosin from IS platelets was significantly lower compared with the activity of the cytoplasmic myosin from normal platelets. These results suggest the presence of a fundamental abnormality of IS platelet contractile proteins.

Recombinant coagulation factor VIIa—a novel haemostatic agent in scoliosis surgery?

“…Although multifactorial in origin, peri-operative haemorrhage associated with spinal fusion techniques results primarily from disruption of internal vertebral veins, decortication of large areas of bone [18], and instrumentation of the vertebrae. Furthermore, haemostatic abnormalities may increase the risk of bleeding in some patients: consumption coagulopathy, dilution coagulopathy caused by normovolaemic haemodilution [29], reduced factor VII (FVII) levels [18], and abnormal platelet aggregation [34,42,44] have all been cited as possible contributors to an increased haemorrhagic tendency. Finally, inferior vena cava tear is a rare but potentially life-threatening cause of bleeding during surgical intervention [43].…”

The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the “metabolic” workgroup of the Fondation Yves Cotrel

“…Platelet function anomalies were identified in AIS patients long ago [42] but the actual relationship with the spinal pathology still remains to be established. Platelets in patients with AIS have elevated levels of Ca 2+ and P i+ [43, 44], decreased activity of intracellular contractile proteins [43, 45], decreased aggregation [26, 46] and abnormal structure of myosin [43]. Interestingly, several studies have demonstrated that intracellular calmodulin levels are also increased, especially in patients with progressive idiopathic scoliosis [47, 48].…”

Platelet calmodulin levels in adolescent idiopathic scoliosis (AIS): can they predict curve progression and severity?

“…Abnormalities in the structure and function of thrombocytes have been noted in patients with AIS by many investigators [7,16,17,18,22,23,24] and reviewed [12,13]. Because the platelet can be considered a "mini" skeletal muscle with a similar protein contractile system (actin and myosin) it follows that both would be affected if a systemic cellular defect was present.…”

“…Where this is the case, an extract of the text is reprinted or a précis is given in a series of comments. Each comment is followed by the respective question(s) and then the answer(s) provided by Lowe. In the early 1980s abnormalities in the structure and function of thrombocytes were noted in patients with AIS [7,16,17,18,22,23,24]. The research of Dr Lowe and his colleagues is predicated on the view that the platelet can be considered a "mini" skeletal muscle with a similar protein contractile system (actin and myosin) so that both would be affected if a systemic cellular defect was present.…”