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Role of the ERK Pat...
Role of the ERK Pathway for Oxidant-Induced Parthanatos in Human Lymphocytes
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- Akhiani, Aliasghar, 1957 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Werlenius, Olle (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för medicin,Institute of Medicine
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- Aurelius, Johan, 1980 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Movitz, Charlotta, 1970 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Martner, Anna, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Hellstrand, Kristoffer, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Bergh Thorén, Fredrik, 1976 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Sahlgrenska Cancer Center,Institute of Biomedicine, Department of Infectious Medicine
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(creator_code:org_t)
- 2014-02-21
- 2014
- Engelska.
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
- Relaterad länk:
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https://gup.ub.gu.se... (primary) (free)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Reactive oxygen species (ROS) are formed by myeloid cells as a defense strategy against microorganisms. ROS however also trigger poly(ADP-ribose) polymerase 1- (PARP-1) dependent cell death (parthanatos) in adjacent lymphocytes, which has been forwarded as a mechanism of immune escape in several forms of cancer. The present study assessed the role of mitogen-activated protein kinases (MAPKs), in particular the extracellular signal-regulated kinase (ERK), in ROS-induced signal transduction leading to lymphocyte parthanatos. We report that inhibitors of ERK1/2 phosphorylation upheld natural killer (NK) cell-mediated cytotoxicity under conditions of oxidative stress and rescued NK cells and CD8(+)T lymphocytes from cell death induced by ROS-producing monocytes. ERK1/2 phosphorylation inhibition also protected lymphocytes from cell death induced by exogenous hydrogen peroxide (H2O2) and from ROS generated by xanthine oxidase or glucose oxidase. Phosphorylation of ERK1/2 was observed in lymphocytes shortly after exposure to ROS. ROS-generating myeloid cells and exogenous H2O2 triggered PARP 1-dependent accumulation of poly ADP-ribose (PAR), which was prevented by ERK pathway inhibitors. ERK1/2 phosphorylation was induced by ROS independently of PARP-1. Our findings are suggestive of a role for ERK1/2 in ROS-induced lymphocyte parthanatos, and that the ERK axis may provide a therapeutic target for the protection of lymphocytes against oxidative stress.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- INDUCED CELL-DEATH
- ACTIVATED PROTEIN-KINASE
- ACUTE MYELOID-LEUKEMIA
- NATURAL-KILLER-CELLS
- REACTIVE OXYGEN METABOLITES
- SIGNAL-REGULATED
- KINASE
- PERIPHERAL T-CELLS
- HYDROGEN-PEROXIDE
- NK CELLS
- HISTAMINE
- DIHYDROCHLORIDE
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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