血红素加氧酶-1抑制促氧化剂诱导的HL-1心肌细胞肥大。
Heme oxygenase-1 inhibits pro-oxidant induced hypertrophy in HL-1 cardiomyocytes.
作者信息
Brunt Keith R, Tsuji Matthew R, Lai Joyce H, Kinobe Robert T, Durante William, Claycomb William C, Ward Christopher A, Melo Luis G
机构信息
Department of Physiology, Queen's University, 431 Botterell Hall, Kingston, Ontario K7L 3N6, Canada.
出版信息
Exp Biol Med (Maywood). 2009 May;234(5):582-94. doi: 10.3181/0810-RM-312. Epub 2009 Feb 25.
AIMS
Reactive oxygen species (ROS) activate multiple signaling pathways involved in cardiac hypertrophy. Since HO-1 exerts potent antioxidant effects, we hypothesized that this enzyme inhibits ROS-induced cardiomyocyte hypertrophy.
METHODS
HL-1 cardiomyocytes were transduced with an adenovirus constitutively expressing HO-1 (AdHO-1) to increase basal HO-1 expression and then exposed to 200 microM hydrogen peroxide (H2O2). Hypertrophy was measured using 3H-leucine incorporation, planar morphometry and cell-size by forward-scatter flow-cytometry. The pro-oxidant effect of H2O2 was assessed by redox sensitive fluorophores. Inducing intracellular redox imbalance resulted in cardiomyocyte hypertrophy through transactivation of nuclear factor kappa B (NF-kappaB).
RESULTS
Pre-emptive HO-1 overexpression attenuated the redox imbalance and reduced hypertrophic indices. This is the first time that HO-1 has directly been shown to inhibit oxidant-induced cardiomyocyte hypertrophy by a NF-kappaB-dependent mechanism.
CONCLUSION
These results demonstrate that HO-1 inhibits pro-oxidant induced cardiomyocyte hypertrophy and suggest that HO-1 may yield therapeutic potential in treatment of.
目的
活性氧（ROS）激活参与心肌肥大的多种信号通路。由于血红素加氧酶-1（HO-1）具有强大的抗氧化作用，我们推测该酶可抑制ROS诱导的心肌细胞肥大。
方法
用组成性表达HO-1的腺病毒（AdHO-1）转导HL-1心肌细胞以增加基础HO-1表达，然后将其暴露于200微摩尔过氧化氢（H2O2）。使用3H-亮氨酸掺入、平面形态测量法以及通过前向散射流式细胞术测量细胞大小来检测肥大情况。通过氧化还原敏感荧光团评估H2O2的促氧化作用。诱导细胞内氧化还原失衡通过核因子κB（NF-κB）的反式激活导致心肌细胞肥大。
结果
预先过表达HO-1可减轻氧化还原失衡并降低肥大指标。这是首次直接证明HO-1通过NF-κB依赖机制抑制氧化剂诱导的心肌细胞肥大。
结论
这些结果表明HO-1抑制促氧化剂诱导的心肌细胞肥大，并提示HO-1可能在治疗中具有治疗潜力。
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