5-aminoimidazole-4-carboxamide Riboside Induces Apoptosis Through AMP-activated Protein Kinase-independent and NADPH Oxidase-dependent Pathways
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It is debatable whether AMP-activated protein kinase(AMPK) activation is involved in anti-apoptotic or pro-apoptoticsignaling. AICAR treatment increases AMPK-α1 phosphorylation,decreases intracellular reactive oxygen species(ROS) levels, and significantly increases Annexin V-positivecells, DNA laddering, and caspase activity in human myeloidcell. AMPK activation is therefore implicated in apoptosis. However, AMPK-α1-knockdown THP-1 cells are more sensitiveto apoptosis than control THP-1 cells are, suggestingthat the apoptosis is AMPK-independent. Low doses ofAICAR induce cell proliferation, whereas high doses ofAICAR suppress cell proliferation. Moreover, these effectsare significantly correlated with the downregulation of intracellularROS, strongly suggesting that AICAR-induced apoptosisis critically associated with the inhibition of NADPH oxidaseby AICAR. Collectively, our results demonstrate that inAICAR-induced apoptosis, intracellular ROS levels are farmore relevant than AMPK activation.
Abstract
It is debatable whether AMP-activated protein kinase(AMPK) activation is involved in anti-apoptotic or pro-apoptoticsignaling. AICAR treatment increases AMPK-α1 phosphorylation,decreases intracellular reactive oxygen species(ROS) levels, and significantly increases Annexin V-positivecells, DNA laddering, and caspase activity in human myeloidcell. AMPK activation is therefore implicated in apoptosis. However, AMPK-α1-knockdown THP-1 cells are more sensitiveto apoptosis than control THP-1 cells are, suggestingthat the apoptosis is AMPK-independent. Low doses ofAICAR induce cell proliferation, whereas high doses ofAICAR suppress cell proliferation. Moreover, these effectsare significantly correlated with the downregulation of intracellularROS, strongly suggesting that AICAR-induced apoptosisis critically associated with the inhibition of NADPH oxidaseby AICAR. Collectively, our results demonstrate that inAICAR-induced apoptosis, intracellular ROS levels are farmore relevant than AMPK activation.
참고문헌 (26)
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