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Alpha-1-microglobulin: Innate defence against pathological oxidation

Gram, Magnus LU (2009) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2009:75.
Abstract
Oxidative stress has been implicated as an important factor in the progression of many diseases. An imbalance in the redox-system may cause oxidation of cells and molecules, which might subsequently lead to tissue damage.

The research presented in this thesis has focused on elucidating a possible involvement of the human protein alpha-1-microglobulin in the defence against pathological oxidation.

alpha-1-microglobulin is a ubiquitous plasma and tissue protein mainly synthesized in the liver. It binds and degrades heme, is a radical scavenger and has reductase properties.

Results in this thesis show that oxidatively challenged cells have the ability to up-regulate their alpha-1-microglobulin de novo synthesis,... (More)
Oxidative stress has been implicated as an important factor in the progression of many diseases. An imbalance in the redox-system may cause oxidation of cells and molecules, which might subsequently lead to tissue damage.

The research presented in this thesis has focused on elucidating a possible involvement of the human protein alpha-1-microglobulin in the defence against pathological oxidation.

alpha-1-microglobulin is a ubiquitous plasma and tissue protein mainly synthesized in the liver. It binds and degrades heme, is a radical scavenger and has reductase properties.

Results in this thesis show that oxidatively challenged cells have the ability to up-regulate their alpha-1-microglobulin de novo synthesis, i.e. human hepatoma and blood cells can up-regulate both their mRNA expression and protein synthesis when exposed to hemoglobin, heme and reactive oxygen species.

Furthermore, alpha-1-microglobulin was shown to exert potent cytoprotective properties against hemoglobin-, heme-, radiation- and reactive oxygen-induced oxidative stress. For instance, alpha-1-microglobulin could reduce cytosol oxidation and formation of molecular oxidation markers in hepatoma cells, blood cells and keratinocytes. Moreover, results show that alpha-1-microglobulin inhibits induction of cellular necrosis and apoptosis.

Finally, hemoglobin, oxidation and alpha-1-microglobulin have been investigated in preeclampsia, a pregnancy-related disease. They were all shown to be elevated, and results suggest that hemoglobin contributes to the oxidative stress seen in preeclampsia.

In conclusion, results presented in this thesis show, for the first time, that alpha-1-microglobulin is involved in the cellular defence against pathological oxidation caused by hemoglobin, heme, radiation and reactive oxygen species. (Less)
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author
supervisor
opponent
  • Professor Wilson, Michael, Department of Biological Sciences
organization
publishing date
type
Thesis
publication status
published
subject
keywords
alpha-1-microglobulin, pathological oxidation, hemoglobin, heme, radiation, oxidation, ROS, hemoglobin and heme antagonist, radical scavenger
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2009:75
pages
58 pages
publisher
Department of Clinical Sciences, Lund University
defense location
GK-salen
defense date
2009-09-11 10:00
ISSN
1652-8220
ISBN
978-91-86253-63-9
language
English
LU publication?
yes
id
68ee35fd-8680-4d65-9cb6-7233be6d0080 (old id 1464287)
date added to LUP
2009-08-19 11:44:16
date last changed
2016-09-19 08:44:51
@phdthesis{68ee35fd-8680-4d65-9cb6-7233be6d0080,
  abstract     = {Oxidative stress has been implicated as an important factor in the progression of many diseases. An imbalance in the redox-system may cause oxidation of cells and molecules, which might subsequently lead to tissue damage.<br/><br>
The research presented in this thesis has focused on elucidating a possible involvement of the human protein alpha-1-microglobulin in the defence against pathological oxidation. <br/><br>
alpha-1-microglobulin is a ubiquitous plasma and tissue protein mainly synthesized in the liver. It binds and degrades heme, is a radical scavenger and has reductase properties. <br/><br>
Results in this thesis show that oxidatively challenged cells have the ability to up-regulate their alpha-1-microglobulin de novo synthesis, i.e. human hepatoma and blood cells can up-regulate both their mRNA expression and protein synthesis when exposed to hemoglobin, heme and reactive oxygen species.<br/><br>
Furthermore, alpha-1-microglobulin was shown to exert potent cytoprotective properties against hemoglobin-, heme-, radiation- and reactive oxygen-induced oxidative stress. For instance, alpha-1-microglobulin could reduce cytosol oxidation and formation of molecular oxidation markers in hepatoma cells, blood cells and keratinocytes. Moreover, results show that alpha-1-microglobulin inhibits induction of cellular necrosis and apoptosis.<br/><br>
Finally, hemoglobin, oxidation and alpha-1-microglobulin have been investigated in preeclampsia, a pregnancy-related disease. They were all shown to be elevated, and results suggest that hemoglobin contributes to the oxidative stress seen in preeclampsia.<br/><br>
In conclusion, results presented in this thesis show, for the first time, that alpha-1-microglobulin is involved in the cellular defence against pathological oxidation caused by hemoglobin, heme, radiation and reactive oxygen species.},
  author       = {Gram, Magnus},
  isbn         = {978-91-86253-63-9},
  issn         = {1652-8220},
  keyword      = {alpha-1-microglobulin,pathological oxidation,hemoglobin,heme,radiation,oxidation,ROS,hemoglobin and heme antagonist,radical scavenger},
  language     = {eng},
  pages        = {58},
  publisher    = {Department of Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Alpha-1-microglobulin: Innate defence against pathological oxidation},
  volume       = {2009:75},
  year         = {2009},
}