Figure 4.

AICAR functions through the activation of AMPK or inhibition of NADPH oxidase in human lymphoid cells. (A and B) Jurkat (A) and THP-1 (B) cells were treated with or without different concentrations of AICAR for different times as indicated. A ³H-thymidine incorporation assay was performed as described in Materials and Methods. Data are the means±SD of the triplicate samples. (C and D) Jurkat (C) and THP-1 (D) cells were treated with or without different concentrations of AICAR for different times as indicated. DCF staining was performed as described in Materials and Methods, and flow cytometry analysis was performed. Data are the averages±SD of the mean fluorescence intensity in triplicate samples. (E) A model for the dual functions of AICAR: AMPK activation and NADPH oxidase inhibition. The activation of AMPK induced by AICAR may initially promote cellular proliferation at early time points (left). However, the inhibition of NADPH oxidase by AICAR induces the downregulation of intracellular ROS levels, which induces cytotoxicity and ultimately apoptosis (right).