Impact of cathepsin A on the murine cardiac proteome

ABSTRACT: Cathepsin A (CTSA) is a lysosomal carboxypeptidase present at the cell surface and secreted outside the cell. Additionally, CTSA binds to β-galactosidase and neuraminidase 1 to protect them from degradation. CTSA has gained attention as a drug target for the treatment of cardiac hypertrophy and heart failure. Here we investigated the impact of CTSA on the murine cardiac proteome in a mouse model of cardiomyocyte-specific human CTSA overexpression, using liquid chromatography-tandem mass spectrometry in conjunction with an isotopic dimethyl labeling strategy. Statistical analysis by linear models for microarray data (limma) found > 300 significantly affected proteins; thus establishing CTSA as a key modulator of the cardiac proteome. CTSA strongly impaired the balance of the proteolytic system by up-regulating several proteases whilst down-regulating numerous protease inhibitors. Moreover, cardiomyocyte-specific human CTSA overexpression strongly reduced the levels of numerous proteins that are involved in the oxidative stress response.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Oliver Schilling  

LAB HEAD: Oliver Schilling

PROVIDER: PXD003860 | Pride | 2016-07-25

REPOSITORIES: Pride