Department of Physiology, Faculty of Medicine, Semmelweis University, PO Box 259, Budapest H-1444, Hungary.
Cardiovasc Res. 2014 Mar 1;101(3):393-9. doi: 10.1093/cvr/cvt256. Epub 2013 Nov 18.
Peroxidases serve diverse biological functions including well-characterized activities in host defence and hormone biosynthesis. More recently, peroxidasin (PXDN) was found to be involved in collagen IV cross-linking in the extracellular matrix (ECM). The aim of this study was to characterize the expression and function of peroxidasin-like protein (PXDNL), a previously unknown peroxidase homologue.
We cloned the PXDNL cDNA from the human heart and identified its expression pattern by northern blot, in situ hybridization, and immunohistochemistry. PXDNL is expressed exclusively in the heart and it has evolved to lose its peroxidase activity. The protein is produced by cardiomyocytes and localizes to cell-cell junctions. We also demonstrate that PXDNL can form a complex with PXDN and antagonizes its peroxidase activity. Furthermore, we show an increased expression of PXDNL in the failing myocardium.
PXDNL is a unique component of the heart with a recently evolved inactivation of peroxidase function. The elevation of PXDNL levels in the failing heart may contribute to ECM dysregulation due to its antagonism of PXDN function.
过氧化物酶具有多种生物学功能，包括在宿主防御和激素生物合成中具有明确特征的活性。最近，过氧化物酶体（PXDN）被发现参与细胞外基质（ECM）中胶原 IV 的交联。本研究旨在表征过氧化物酶样蛋白（PXDNL）的表达和功能，PXDNL 是一种以前未知的过氧化物酶同源物。
我们从人心脏中克隆了 PXDNL cDNA，并通过 northern blot、原位杂交和免疫组织化学鉴定了其表达模式。PXDNL 仅在心脏中表达，其进化过程中失去了过氧化物酶活性。该蛋白由心肌细胞产生，并定位于细胞-细胞连接处。我们还证明 PXDNL 可以与 PXDN 形成复合物并拮抗其过氧化物酶活性。此外，我们还显示在衰竭的心肌中 PXDNL 的表达增加。
PXDNL 是心脏的独特组成部分，其过氧化物酶功能最近才发生了失活。衰竭心脏中 PXDNL 水平的升高可能会由于其拮抗 PXDN 功能而导致 ECM 失调。
