| Full text | |
| Author(s): Show less - |
Cruz, Litiele Cezar
;
Habibovic, Aida
;
Dempsey, Bianca
;
Massafera, Mariana P.
;
Janssen-Heininger, Yvonne M. W.
;
Lin, Miao-chong Joy
;
Hoffman, Evan T.
;
Weiss, Daniel J.
;
Huang, Steven K.
;
van der Vliet, Albert
;
Meotti, Flavia C.
Total Authors: 11
|
| Document type: | Journal article |
| Source: | REDOX BIOLOGY; v. 71, p. 13-pg., 2024-03-01. |
| Abstract | |
Peroxidasin (PXDN) is a secreted heme peroxidase that catalyzes the oxidative crosslinking of collagen IV within the extracellular matrix (ECM) via intermediate hypobromous acid (HOBr) synthesis from hydrogen peroxide and bromide, but recent findings have also suggested alternative ECM protein modifications by PXDN, including incorporation of bromide into tyrosine residues. In this work, we sought to identify the major target proteins for tyrosine bromination by HOBr or by PXDN mediated oxidation in ECM from mouse teratocarcinoma PFHR9 cells. We detected 61 bromotyrosine (BrY)-containing peptides representing 23 proteins in HOBr-modified ECM from PFHR9 cells, among which laminins displayed the most prominent bromotyrosine incorporation. Moreover, we also found that laminin alpha 1, laminin beta 1, and tubulointerstitial nephritis antigen-like (TINAGL1) contained BrY in untreated PFHR9 cells, which depended on PXDN. We extended these analyses to lung tissues from both healthy mice and mice with experimental lung fibrosis, and in lung tissues obtained from human subjects. Analysis of ECM-enriched mouse lung tissue extracts showed that 83 ECM proteins were elevated in bleomycin-induced fibrosis, which included various collagens and laminins, and PXDN. Similarly, mRNA and protein expression of PXDN and laminin alpha/beta 1 were enhanced in fibrotic mouse lung tissues, and also in mouse bone-marrow-derived macrophages or human fibroblasts stimulated with transforming growth factor beta 1, a profibrotic growth factor. We identified 11 BrY-containing ECM proteins, including collagen IV alpha 2, collagen VI alpha 1, TINAGL1, and various laminins, in both healthy and mouse fibrotic lung tissues, although the relative extent of tyrosine bromination of laminins was not significantly increased during fibrosis. Finally, we also identified 7 BrY-containing ECM proteins in human lung tissues, again including collagen IV alpha 2, collagen VI alpha 1, and TINAGL1. Altogether, this work demonstrates the presence of several bromotyrosine-modified ECM proteins, likely involving PXDN, even in normal lung tissues, suggesting a potential biological function for these modifications. (AU) | |
| FAPESP's process: | 18/14898-2 - Investigations of the redox processes in inflammatory response and associated pathologies |
| Grantee: | Flavia Carla Meotti |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| FAPESP's process: | 12/12663-1 - Singlet molecular oxygen and peroxides in chemical biology |
| Grantee: | Paolo Di Mascio |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |