A1M/α1-microglobulin is proteolytically activated by myeloperoxidase, binds its heme group and inhibits low density lipoprotein oxidation.
(2015) In Frontiers in Physiology 6.- Abstract
- α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a... (More)
- α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a regulator of its activity. The results show that A1M is proteolytically cleaved, with formation of t-A1M, after exposure to MPO, and that t-A1M contains iron and heme-degradation products. The reaction is dependent of pH, time and concentration of substrates and a pH-value around 7 is shown to be optimal for cleavage. Furthermore, A1M inhibits MPO- and hydrogen peroxide-induced oxidation of LDL. The results suggest that A1M may have a role as an inhibitor of the damaging effects of the neutrophil respiratory burst on bystander tissue components. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5143190
- author
- Cederlund, Martin LU ; Deronic, Adnan LU ; Pallon, Jan LU ; Sørensen, Ole E LU and Åkerström, Bo LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Frontiers in Physiology
- volume
- 6
- article number
- 11
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:25698971
- wos:000349291500001
- scopus:84926453297
- pmid:25698971
- ISSN
- 1664-042X
- DOI
- 10.3389/fphys.2015.00011
- language
- English
- LU publication?
- yes
- id
- 3c9273a0-d18f-4d85-be85-127176178a1d (old id 5143190)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25698971?dopt=Abstract
- date added to LUP
- 2016-04-01 12:54:03
- date last changed
- 2022-03-06 02:38:35
@article{3c9273a0-d18f-4d85-be85-127176178a1d, abstract = {{α1-microglobulin (A1M) is a 26 kDa plasma and tissue protein with reductase activity and radical- and heme-binding anti-oxidative functions. In addition, exposure of A1M to hemoglobin has been shown to induce proteolytic elimination of a C-terminal tetrapeptide yielding a heme-degrading form, truncated A1M (t-A1M). Myeloperoxidase (MPO), a heme-containing enzyme that catalyzes the production of free radicals and hypochlorite, is released by neutrophils during the inflammatory response to bacterial infections. MPO-induced low density lipoprotein (LDL)-oxidation in blood has been suggested as a causative factor in atherosclerosis. In this study we have hypothesized that A1M interacts with MPO in a similar mode as with hemoglobin, and is a regulator of its activity. The results show that A1M is proteolytically cleaved, with formation of t-A1M, after exposure to MPO, and that t-A1M contains iron and heme-degradation products. The reaction is dependent of pH, time and concentration of substrates and a pH-value around 7 is shown to be optimal for cleavage. Furthermore, A1M inhibits MPO- and hydrogen peroxide-induced oxidation of LDL. The results suggest that A1M may have a role as an inhibitor of the damaging effects of the neutrophil respiratory burst on bystander tissue components.}}, author = {{Cederlund, Martin and Deronic, Adnan and Pallon, Jan and Sørensen, Ole E and Åkerström, Bo}}, issn = {{1664-042X}}, language = {{eng}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Physiology}}, title = {{A1M/α1-microglobulin is proteolytically activated by myeloperoxidase, binds its heme group and inhibits low density lipoprotein oxidation.}}, url = {{https://lup.lub.lu.se/search/files/3033235/8056933}}, doi = {{10.3389/fphys.2015.00011}}, volume = {{6}}, year = {{2015}}, }