Quiescin sulfhydryl oxidase (QSOX) is expressed in the human atheroma core: possible role in apoptosis

Abstract

Quiescin sulfhydryl oxidases (QSOXs) catalyze the formation of disulfide bonds in peptides and proteins, and in vertebrates comprise two proteins: QSOX1 and QSOX2. QSOX1, the most extensively studied type, has been implicated in protein folding, production of extracellular matrix, redox regulation, protection from apoptosis, angiogenesis, and cell differentiation. Atherosclerosis is an immunopathological condition in which redox processes, apoptosis, cell differentiation, and matrix secretion/maturation have critical roles. Considering these data, we hypothesized that QSOX1 could be involved in this disease, possibly reducing apoptosis and angiogenesis inside the plaque. QSOX1 labeling in normal human carotid vessels showed predominant expression by endothelium, subendothelium, and adventitia. In atherosclerotic plaques, however, QSOX1 was highly expressed in macrophages at the lipid core. QSOX1 expression was also studied in terms of mRNA and protein in cell types present in plaques under apoptotic or activating stimuli, emulating conditions found in the atherosclerotic process. QSOX1 mRNA increased in endothelial cells and macrophages after the induction of apoptosis. At the protein level, the correlation between apoptosis and QSOX1 expression was not evident in all cell types, possibly because of a rapid secretion of QSOX1. Our results propose for the first time possible roles for QSOX1 in atherosclerosis, being upregulated in endothelial cells and macrophages by apoptosis and cell activation, and possibly controlling these processes, as well as angiogenesis. The quantitative differences in QSOX1 induction may depend on the cell type and also on local factors.

Elevated Transcription of the Gene QSOX1 Encoding Quiescin Q6 Sulfhydryl Oxidase 1 in Breast Cancer

“…Although initially identified as being strongly up-regulated in fibroblasts reaching confluence, it has also been since associated with growth factor activity, and it is highly expressed in cells with a large secretory load [12]. In different studies on QSOX1 a variety of functions have been ascribed to this enzyme including protection from apoptosis [11], [12], [39]–[42] and facilitation of tumour cells invasion [38]. Thus, the forced overexpression of quiescin 6 in human MCF-7 breast cancer cells rendered them more resistant to apoptosis arising from oxidative stress compared to control transfected cells, thereby implicating QSOX1 in cell survival [11] whilst the suppressed expression of quiescin in pancreatic cancer cell lines BxPC-3 and Panc-1 inhibited cancer cell invasion by activation of MMP-2 and MMP-9 Matrix Metalloproteinases [43].…”

Diagnostic and predictive values of ferroptosis-related genes in heart failure

“…It is necessary for correct protein folding in the endosome or sarcoplasmic reticulum, which is required for abrogation and protective reactions during acute stress [28] . Additionally expressed in the human atherosclerotic core, quiescence sulfhydryl oxidase (QSOX) may be involved in apoptosis [29] . Through several redox pathways, quiescent in sulfhydryl oxidase 1b (QSOX1b) stimulates the migration and proliferation of vascular smooth muscle cells [30] .…”

Ferroptosis in Cancer Immunotherapy—Implications for Hepatocellular Carcinoma

“…Blocks system x c − activity via binding of SLC7A11 [117] human colorectal cancer cell lines (HCT116, CX-1, LoVo, SW48) [118] Human pancreatic cancer cell line (PANC1) [119] human fibrosarcoma cell line (HT1080) [119] human non-small-cell lung cancer cell line (Calu-1) [119] human synovial sarcoma cell line (SW982) [120] Induction human colon cancer xenograft mice (HT-29) [121] human fibrosarcoma xenograft mice (HT1080) [119] NRF2 Key regulator of antioxidant response including system x c − -expression [122] human lung cell lines (H460, H1975, H1299,95D, A549) [123] human hepatocellular carcinoma cell lines (Hep3B, Bel-7402, and HepG2) [124] human breast carcinoma cell line (MDA-MB-231) [125] human neuroblastoma cell line (SH-SY5Y) [125] Inhibition human lung cancer xenograft mice [123] QSOX1 Inhibition of NRF2 activation [126] human hepatocellular carcinoma cell lines (HCC-LM3, MHCC97L, MHCC97H, SMMC7721, SMMC-7402, HuH7, PLC, Hep3B, HepG2) [127] cervical carcinoma cell line (HeLa) [128] human breast carcinoma cell line (BT549, BT474) [129] human kidney carcinoma cell line (786-O) [130] Induction human primary breast tumor clinical study [131] human kidney carcinoma xenograft mice [130] BCAT2 Regulates intracellular glutamate concentration [132] murine hepatocellular carcinoma cell line (H22) [132] murine pancreatic carcinoma cell line (Panc02) [132] human pancreas carcinoma cell line (AsPC-1) [132] human hepatocellular carcinoma cell line (HepG2) [132] human fibrosarcoma cell line (HT1080) [132] human colon cancer cell line (SW-480) [132] patient-derived human breast carcinoma cell line (BCC, MCF-7) [133] human ovarian cancer cell line (HeLa) [134] human colon cancer cell line (HCT116) [134] Inhibition hepatocellular carcinoma xenograf...…”