Adipocyte differentiation in Sod2^−/− and Sod2^+/+ murine bone marrow stromal cells is associated with low antioxidant pools

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• 作者：Stanislav Lechpammer ; Michael W. Epperly ; Shuanhu Zhou ; Suhua Nie ; Julie Glowacki and Joel S. Greenberger
• 刊名：Experimental Hematology
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：33
• 期：10
• 页码：1201-1208
• 全文大小：376 K

文摘

Objective

Adipocytogenesis in bone marrow stromal cells (BMSCs) from manganese-superoxide dismutase–deficient (Sod2^−/−) and wild-type (Sod2^+/+) mice and the effect of antioxidant pool size were determined.

Methods

BMSCs from Sod2^−/− or Sod2^+/+ mice were cultured with and without adipocytogenic supplements including: 10 μg/mL insulin, 1 μM dexamethasone, and 100 μM indomethacin. Oil Red-O-positive cells and reverse-transcriptase polymerase chain reaction measurement of peroxisome proliferator-activated receptor-γ (PPARγ) and lipoprotein lipase (LPL) were measured. Antioxidant glutathione levels (GSH) and glutathione peroxidase activity (GPX) were determined.

Results

Sod2^−/− cells demonstrated constitutive adipocytogenesis in basal medium and generated 34 % more adipocytes in adipocytogenic media. Growth of cells in the free radical scavenger antioxidant, amifostine (WR2721; 4 mM) decreased numbers of adipocytes in Sod2^−/− BMSCs in both basal (38.0 % , p = 0.037) and adipocytogenic (37.5 % , p = 0.021) media and reduced to undetectable the levels of expression of PPARγ and LPL. In contrast, Sod2^+/+ cells showed no detectable constitutive adipocytogenesis but formed adipocytes in adipocytogenic medium, with a decrease (43.7 % , p = 0.001) by addition of WR2721. In basal conditions, Sod2^−/− cells had lower GSH (78.6 % ; p = 0.0089) and GPX (52.7 % ; p < 0.001) levels than did Sod2^+/+ cells, which were increased in either medium by WR2721 treatment of Sod2^−/− or Sod2^+/+ cells (all p < 0.001). Differentiation of BMSCs to adipocytes was inversely correlated with the level of GSH (r = −0.9427, p = 0.0167). Sod2^−/− long-term bone marrow cultures had decreased hematopoiesis compared to those from Sod2^+/− or Sod2^+/+ mice.

Conclusion

The cellular redox pathway has a role in adipocyte differentiation of cells of the hematopoietic microenvironment.