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5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways
It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-α1 phosphorylation, decreases intracellular reactive oxygen species (ROS) levels, and significantly increases Annexin V-positive cells, DNA...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Association of Immunologists
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212085/ https://www.ncbi.nlm.nih.gov/pubmed/25360075 http://dx.doi.org/10.4110/in.2014.14.5.241 |
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author | Wi, Sae Mi Lee, Ki-Young |
author_facet | Wi, Sae Mi Lee, Ki-Young |
author_sort | Wi, Sae Mi |
collection | PubMed |
description | It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-α1 phosphorylation, decreases intracellular reactive oxygen species (ROS) levels, and significantly increases Annexin V-positive cells, DNA laddering, and caspase activity in human myeloid cell. AMPK activation is therefore implicated in apoptosis. However, AMPK-α1-knockdown THP-1 cells are more sensitive to apoptosis than control THP-1 cells are, suggesting that the apoptosis is AMPK-independent. Low doses of AICAR induce cell proliferation, whereas high doses of AICAR suppress cell proliferation. Moreover, these effects are significantly correlated with the downregulation of intracellular ROS, strongly suggesting that AICAR-induced apoptosis is critically associated with the inhibition of NADPH oxidase by AICAR. Collectively, our results demonstrate that in AICAR-induced apoptosis, intracellular ROS levels are far more relevant than AMPK activation. |
format | Online Article Text |
id | pubmed-4212085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Korean Association of Immunologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-42120852014-10-30 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways Wi, Sae Mi Lee, Ki-Young Immune Netw Original Article It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-α1 phosphorylation, decreases intracellular reactive oxygen species (ROS) levels, and significantly increases Annexin V-positive cells, DNA laddering, and caspase activity in human myeloid cell. AMPK activation is therefore implicated in apoptosis. However, AMPK-α1-knockdown THP-1 cells are more sensitive to apoptosis than control THP-1 cells are, suggesting that the apoptosis is AMPK-independent. Low doses of AICAR induce cell proliferation, whereas high doses of AICAR suppress cell proliferation. Moreover, these effects are significantly correlated with the downregulation of intracellular ROS, strongly suggesting that AICAR-induced apoptosis is critically associated with the inhibition of NADPH oxidase by AICAR. Collectively, our results demonstrate that in AICAR-induced apoptosis, intracellular ROS levels are far more relevant than AMPK activation. The Korean Association of Immunologists 2014-10 2014-10-22 /pmc/articles/PMC4212085/ /pubmed/25360075 http://dx.doi.org/10.4110/in.2014.14.5.241 Text en Copyright © 2014 The Korean Association of Immunologists http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Wi, Sae Mi Lee, Ki-Young 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways |
title | 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways |
title_full | 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways |
title_fullStr | 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways |
title_full_unstemmed | 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways |
title_short | 5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways |
title_sort | 5-aminoimidazole-4-carboxamide riboside induces apoptosis through amp-activated protein kinase-independent and nadph oxidase-dependent pathways |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212085/ https://www.ncbi.nlm.nih.gov/pubmed/25360075 http://dx.doi.org/10.4110/in.2014.14.5.241 |
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