5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways.
- Author:
Sae Mi WI
1
;
Ki Young LEE
Author Information
- Publication Type:Original Article
- Keywords: 5-aminoimidazole-4-carboxamide (AICA) riboside; AMP-activated protein kinase; Apoptosis; NADPH oxidase; Reactive oxygen species; Lymphoid cells
- MeSH: AMP-Activated Protein Kinases; Apoptosis*; Cell Proliferation; DNA; Down-Regulation; Humans; Lymphocytes; Myeloid Cells; NADP*; NADPH Oxidase; Phosphorylation; Reactive Oxygen Species
- From:Immune Network 2014;14(5):241-248
- CountryRepublic of Korea
- Language:English
- Abstract: It is debatable whether AMP-activated protein kinase (AMPK) activation is involved in anti-apoptotic or pro-apoptotic signaling. AICAR treatment increases AMPK-alpha1 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-alpha1-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.
