Mutations in Parkin gene are responsible of 50% of cases with autosomal recessive juvenile-onset Parkinson’s disease (ARJP). Although 21 parkin alternative splice variants have been cloned so far, most of the studies have focused their attention on the full-length protein. Despite the expression of the originally cloned protein has been observed in human blood cells, there is currently no study that has investigated the expression profile of parkin isoforms in human lymphomonocyte (LMN). In the present study, we have explored the expression pattern of parkin proteins in total LMN and in specific subpopulations like T lymphocyte (CD2+), monocyte (CD14+) and B lymphocyte (CD19+). Peripheral blood was collected from healthy volunteers (n=5). Total LMN homogenate expresses H1, H5 and H6 parkin isoforms. These data have been confirmed by immunoprecipitation analysis, by using three antibodies recognizing different domains of the full-length. In human CD2+, CD14+ and CD19+ subpopulations, two bands of ~58 and ~52 kDa molecular weight have been revealed. These proteins are distributed both in cytoplasm and nucleus, as demonstrated by fluorescence immunolocalization. The expression of parkin isoforms in human blood cells is subpopulation-specific, and is likely altered in PD patients. A future investigation of the parkin splicing profile in human blood cells could represent a useful tool for identify early non-invasive biomarkers in patients affected by ARJP.

Expression Profile of Human PARK2 Splicing Isoforms in Peripheral Blood Cells and Isolated Lymphomonocytes

D'Amico A;
2016

Abstract

Mutations in Parkin gene are responsible of 50% of cases with autosomal recessive juvenile-onset Parkinson’s disease (ARJP). Although 21 parkin alternative splice variants have been cloned so far, most of the studies have focused their attention on the full-length protein. Despite the expression of the originally cloned protein has been observed in human blood cells, there is currently no study that has investigated the expression profile of parkin isoforms in human lymphomonocyte (LMN). In the present study, we have explored the expression pattern of parkin proteins in total LMN and in specific subpopulations like T lymphocyte (CD2+), monocyte (CD14+) and B lymphocyte (CD19+). Peripheral blood was collected from healthy volunteers (n=5). Total LMN homogenate expresses H1, H5 and H6 parkin isoforms. These data have been confirmed by immunoprecipitation analysis, by using three antibodies recognizing different domains of the full-length. In human CD2+, CD14+ and CD19+ subpopulations, two bands of ~58 and ~52 kDa molecular weight have been revealed. These proteins are distributed both in cytoplasm and nucleus, as demonstrated by fluorescence immunolocalization. The expression of parkin isoforms in human blood cells is subpopulation-specific, and is likely altered in PD patients. A future investigation of the parkin splicing profile in human blood cells could represent a useful tool for identify early non-invasive biomarkers in patients affected by ARJP.
Parkin protein; T lymphocyte; B lymphocyte
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.12078/1625
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