Fully processed lysyl oxidase catalyst translocates from the extracellular space into nuclei of aortic smooth-muscle cells

Abstract

Lysyl oxidase (LO), a secreted protein, was recently identified within the nuclei of vascular smooth-muscle cells (SMC) and 3T3 fibroblasts. A possible pathway by which LO can enter cell nuclei was explored in the present study. SMC were incubated with purified 32-kDa bovine aorta LO that had been fluorescently labeled with rhodamine (TRITC-LO). TRITC-LO entered the cytosol and then rapidly concentrated within the nuclei of preconfluent cultures of these cells, whereas carbonic anhydrase, a protein of similar molecular weight and similarly labeled, did not enter the cells under these conditions. LO that had been reductively methylated at lysine residues with [(14)C]HCHO was also taken up into the cytosolic and nuclear compartments. Intracellular uptake and intracellular distribution were not altered by inhibiting LO activity with beta-aminopropionitrile. An excess of native LO but not of carbonic anhydrase competitively inhibited the uptake of the isotopically labeled enzyme. Thus, once secreted and proteolytically processed, mature LO can enter the cells and concentrate within nuclei in a manner that appears to be specific and independent of its catalytic activity.

Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia

“…LOX enters the cells and moves into nuclei in a manner that appears to be independent of its catalytic activity, as previously reported [49]. In this study, LOX-positive gastric cancer was found to be associated with tumor cell invasion, Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer… 439 lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal dissemination.…”

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“…Kagan et al first documented the presence and retained catalytic activity of LOX mature enzyme within the nuclei of rat vascular smooth muscle cells and NIH 3T3 fibroblasts [23]. Later, it was demonstrated that exogenous mature LOX enzyme could enter the cells and concentrate within the nuclei [24]. Here for the first time, our results demonstrated the existence of LOX proenzyme (50kDa) and mature enzyme (32kDa) within the nuclei of colon cancer cells.…”

Autocrine Growth Factor Regulation of Lysyl Oxidase Expression in Transformed Fibroblasts

“…Mature lysyl oxidase enzyme has been reported to be taken up by cells and translocated to the nucleus of some cells, where it influences the transcription of type III collagen (67)(68)(69). It has been suggested that lysyl oxidase could interact with histones (70), known in vitro substrates of purified lysyl oxidase (71), and thereby possibly directly or indirectly regulate gene transcription.…”