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Differences in the resting platelet proteome and platelet releasate between healthy children and adults
Charmaine Cini1, Christina Yip2, Chantal Attard1
1Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.
Insights
Platelets show distinct protein expression differences between children and adults, offering insights into disease development and protective mechanisms. These findings advance our understanding of platelet physiology in growth and aging.
Area of Science:
- Proteomics
- Molecular Biology
- Human Physiology
Background:
- Major age-related diseases like cardiovascular disease and cancer are leading causes of death globally.
- Children exhibit a lower incidence of such diseases, suggesting inherent protective mechanisms.
- Previous studies identified age-related differences in plasma proteomes, with many proteins originating from platelets.
Purpose of the Study:
- To compare the resting platelet proteome and platelet releasate between healthy children and adults.
- To establish a proteomic analysis procedure for pediatric platelets.
- To identify age-specific differences in platelet protein expression.
Main Methods:
- Proteomic analysis of platelets using Two-dimensional Differential In-Gel Electrophoresis and mass spectrometry.
- Comparison of protein expression in resting platelets and platelet releasate from children and adults.
Main Results:
- Nine proteins (1.1%) showed differential expression in the resting platelet proteome of children versus adults.
- Serotransferrin, fibrinogen alpha chain, and albumin were upregulated in children, while thrombospondin-1 was downregulated.
- Eleven proteins (1.5%) were differentially expressed in the platelet releasate, with transferrin upregulated and TSP-1 downregulated in children.
Conclusions:
- Significant age-specific differences exist in platelet protein expression.
- These identified proteins are involved in crucial processes like tissue development, cell proliferation, and angiogenesis.
- The findings provide novel insights into platelet physiology and its role in growth, development, and aging.
Abstract:
Major age-related diseases such as cardiovascular disease and cancer are the primary causes of morbidity and mortality in Australia and worldwide. In our recent study characterising differences in the plasma proteome between healthy children and adults, a large number of proteins differentially expressed with age were found to be of platelet origin. This study aimed to characterise differences in the resting platelet proteome and the platelet releasate of healthy children compared to healthy adults. This study represents the setup of a procedure for the proteomic analysis of platelets from children. Differentially expressed platelet proteins were identified using Two-dimensional Differential In-Gel Electrophoresis and mass spectrometry. Significant differences in the expression of nine proteins (1.1%) in the resting platelet proteome were observed in children compared to adults. Serotransferrin, fibrinogen alpha chain, glyceraldehyde-3 phosphate dehydrogenase, serum albumin, transgelin-2, calponin-2/LIM and SH3 domain protein 1 and human chorionic gonadotropin 2039797 were up-regulated, whereas thrombospondin-1 was down-regulated in children. Eleven proteins (1.5%) were differentially expressed in the platelet releasate of children compared to adults, where transferrin was also upregulated and TSP-1 was down regulated. Identified proteins are involved in processes including tissue and organ development, cell proliferation regulation and angiogenesis. Our results provide novel insights into platelet physiology as well as growth, development and ageing in healthy individuals.
Biological Significance:
The incidence of major diseases such as cardiovascular disease (CVD) and cancer increase with increasing age and are the major causes of morbidity and mortality both in Australia and worldwide. As the aged population continues to increase dramatically, so too will the financial strains associated with the long term care of the elderly population. Compared to adults, children have a significantly lower incidence of major diseases such as thromboembolic disease. This suggests that children have a protective mechanism against the development of disease. Therefore, studies focussing on the molecular changes of proteins, the machinery of the cell, between children and adults are the key to determining the underlying mechanisms responsible for the onset of major diseases. A well-defined example of how protein expression can change with age is that of the plasma proteome. Significant differences in the expression of numerous plasma proteins between healthy children and adults have been recently demonstrated. Interestingly, a large number of differentially expressed proteins were found to be of platelet origin. This finding forms the basis for the current study, presenting as strong evidence for the age-specific differences of the platelet proteome.
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