GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu
Jerotic, D
Suvakov, S
Matic, M
Alqudah, A
Grieve, DJ
Pljesa-Ercegovac, M
Savic-Radojevic, A
Damjanovic, T
Dimkovic, N
McClements, L
Simic, T
- Publisher:
- HINDAWI LTD
- Publication Type:
- Journal Article
- Citation:
- Oxidative Medicine and Cellular Longevity, 2021, 2021, pp. 6678924
- Issue Date:
- 2021-01-25
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Jerotic, D | |
dc.contributor.author | Suvakov, S | |
dc.contributor.author | Matic, M | |
dc.contributor.author | Alqudah, A | |
dc.contributor.author | Grieve, DJ | |
dc.contributor.author | Pljesa-Ercegovac, M | |
dc.contributor.author | Savic-Radojevic, A | |
dc.contributor.author | Damjanovic, T | |
dc.contributor.author | Dimkovic, N | |
dc.contributor.author |
McClements, L https://orcid.org/0000-0002-4911-1014 |
|
dc.contributor.author | Simic, T | |
dc.date.accessioned | 2022-01-12T08:28:40Z | |
dc.date.available | 2020-12-26 | |
dc.date.available | 2022-01-12T08:28:40Z | |
dc.date.issued | 2021-01-25 | |
dc.identifier.citation | Oxidative Medicine and Cellular Longevity, 2021, 2021, pp. 6678924 | |
dc.identifier.issn | 1942-0900 | |
dc.identifier.issn | 1942-0994 | |
dc.identifier.uri | http://hdl.handle.net/10453/153006 | |
dc.description.abstract | Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD. | |
dc.format | Electronic-eCollection | |
dc.language | eng | |
dc.publisher | HINDAWI LTD | |
dc.relation.ispartof | Oxidative Medicine and Cellular Longevity | |
dc.relation.isbasedon | 10.1155/2021/6678924 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 11 Medical and Health Sciences | |
dc.subject.mesh | Biomarkers | |
dc.subject.mesh | Cytokines | |
dc.subject.mesh | Gene Deletion | |
dc.subject.mesh | Glutathione Peroxidase | |
dc.subject.mesh | Glutathione Transferase | |
dc.subject.mesh | Human Umbilical Vein Endothelial Cells | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Intercellular Adhesion Molecule-1 | |
dc.subject.mesh | Kidney Failure, Chronic | |
dc.subject.mesh | Malondialdehyde | |
dc.subject.mesh | Oxidative Stress | |
dc.subject.mesh | Proteome | |
dc.subject.mesh | Reactive Oxygen Species | |
dc.subject.mesh | Superoxide Dismutase | |
dc.subject.mesh | Uremia | |
dc.subject.mesh | Vascular Cell Adhesion Molecule-1 | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Kidney Failure, Chronic | |
dc.subject.mesh | Uremia | |
dc.subject.mesh | Reactive Oxygen Species | |
dc.subject.mesh | Malondialdehyde | |
dc.subject.mesh | Glutathione Peroxidase | |
dc.subject.mesh | Superoxide Dismutase | |
dc.subject.mesh | Glutathione Transferase | |
dc.subject.mesh | Intercellular Adhesion Molecule-1 | |
dc.subject.mesh | Vascular Cell Adhesion Molecule-1 | |
dc.subject.mesh | Proteome | |
dc.subject.mesh | Cytokines | |
dc.subject.mesh | Gene Deletion | |
dc.subject.mesh | Oxidative Stress | |
dc.subject.mesh | Human Umbilical Vein Endothelial Cells | |
dc.subject.mesh | Biomarkers | |
dc.title | GSTM1 Modulates Expression of Endothelial Adhesion Molecules in Uremic Milieu | |
dc.type | Journal Article | |
utslib.citation.volume | 2021 | |
utslib.location.activity | United States | |
utslib.for | 11 Medical and Health Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2022-01-12T08:28:37Z | |
pubs.publication-status | Published online | |
pubs.volume | 2021 |
Abstract:
Deletion polymorphism of glutathione S-transferase M1 (GSTM1), a phase II detoxification and antioxidant enzyme, increases susceptibility to end-stage renal disease (ESRD) as well as the development of cardiovascular diseases (CVD) among ESRD patients and leads to their shorter cardiovascular survival. The mechanisms by which GSTM1 downregulation contributes to oxidative stress and inflammation in endothelial cells in uremic conditions have not been investigated so far. Therefore, the aim of the present study was to elucidate the effects of GSTM1 knockdown on oxidative stress and expression of a panel of inflammatory markers in human umbilical vein endothelial cells (HUVECs) exposed to uremic serum. Additionally, we aimed to discern whether GSTM1-null genotype is associated with serum levels of adhesion molecules in ESRD patients. HUVECs treated with uremic serum exhibited impaired redox balance characterized by enhanced lipid peroxidation and decreased antioxidant enzyme activities, independently of the GSTM1 knockdown. In response to uremic injury, HUVECs exhibited alteration in the expression of a series of inflammatory cytokines including retinol-binding protein 4 (RBP4), regulated on activation, normal T cell expressed and secreted (RANTES), C-reactive protein (CRP), angiogenin, dickkopf-1 (Dkk-1), and platelet factor 4 (PF4). GSTM1 knockdown in HUVECs showed upregulation of monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in the regulation of monocyte migration and adhesion. These cells also have shown upregulated intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). In accordance with these findings, the levels of serum ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) were increased in ESRD patients lacking GSTM1, in comparison with patients with the GSTM1-active genotype. Based on these results, it may be concluded that incubation of endothelial cells in uremic serum induces redox imbalance accompanied with altered expression of a series of cytokines involved in arteriosclerosis and atherosclerosis. The association of GSTM1 downregulation with the altered expression of adhesion molecules might be at least partly responsible for the increased susceptibility of ESRD patients to CVD.
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