Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor FoxO.
Repression of excessive increase and enlargement of adipocytes that is closely associated with obesity is effective in the prevention and treatment of metabolic syndrome. Generally, apoptosis is induced in cells via a wide variety of intracellular or extracellular substances, and recently, it has been suggested that the FoxO subfamily is involved in the induction of apoptosis. We aimed to elucidate the mechanism of FoxO-mediated apoptosis-induction in the adipocytes under the reactive oxygen species (ROS) stimulus. The treatment of differentiated and undifferentiated 3T3-L1 cells with glucose oxidase (GOD), an enzyme that generates H(2)O(2), induced apoptosis and led to the accumulation of 8-OHdG. Apoptosis analysis revealed that GOD treatment induced apoptosis in differentiated 3T3-L1 cells less efficiently than in undifferentiated preadipocytes. GOD remarkably increased the levels of Bad, Bax, and Bim-the genes that are actively involved in cell apoptosis. GOD treatment also increased the expression of FoxO3a mRNA and protein. The introduction of FoxO3a-siRNA into 3T3-L1 cells suppressed the oxidative stress-induced expression of Bim mRNA, as well as the GOD-induced apoptosis. Furthermore, the expression of MnSOD, Cu/ZnSOD, and catalase, as well as of FoxO, increased significantly along with the progression of adipocyte differentiation. These results indicated that ROS-induced apoptosis in undifferentiated 3T3-L1 cells via the expression of FoxO3a, whereas FoxO expression suppressed the ROS-induced apoptosis in differentiated 3T3-L1 cells via the expression of ROS-scavenging enzymes.
Kojima
Takayuki
T
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
Norose
Takanari
T
Tsuchiya
Keita
K
Sakamoto
Kazuichi
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress
D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D006861:Hydrogen Peroxide