Thioredoxin, a redox-regulating protein, is expressed in spontaneous myocarditis in inbred strains of mice.

Thioredoxin, a redox-regulating protein, is expressed in spontaneous myocarditis in inbred strains of mice.
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DOI:
10.1016/j.ijcard.2003.10.009
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发表时间:
2004-06
影响因子:
3.5
通讯作者:
M. Miyamoto;C. Kishimoto;Masaomi Nimata;Hajime Nakamura;J. Yodoi
M. Miyamoto;C. Kishimoto;Masaomi Nimata;Hajime Nakamura;J. Yodoi
中科院分区:
医学2区
文献类型:
--
作者:
M. Miyamoto;C. Kishimoto;Masaomi Nimata;Hajime Nakamura;J. Yodoi

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氧化还原调节机制可能参与了衰老的发病机制。硫氧还蛋白(Trx)是一种含有氧化还原活性序列的多功能小蛋白。自发性心肌炎常见于老年小鼠。在这项研究中,我们研究了自发性心肌炎近交系小鼠的组织病理学和TRX表达的特点。4周龄成年近交系小鼠未发现自发性心肌炎。8周龄DBA/2小鼠自发性心肌炎发生率较高,8周龄BALB/c或C57BL/6小鼠自发性心肌炎发生率较低。病变局限于右心室,DBA/2小鼠的病变最为严重。Trx在这些菌株中表达上调,并且其表达与疾病的严重程度相关。此外,8-羟基-2‘-脱氧鸟苷(8-OHdG),这是一个公认的氧化应激标志,在其中的坏死性病变中也呈阳性。此外,长期使用N-乙酰半胱氨酸(NAC)的抗氧化治疗抑制了自发性心肌炎的发展。因此,TRX可能是由自发性心肌炎引起的,氧化还原调节系统可能在增龄性心肌炎的发生发展中起重要作用。
Redox-regulating mechanisms may be involved in the pathogenesis of aging. Thioredoxin (TRX) is a small multifunctional protein which contains a redox active sequence. Spontaneous myocarditis is often observed in aged mice. In this study, we examined the histopathology and characteristics of TRX expression in spontaneous myocarditis in inbred strains of mice. No spontaneous myocarditis was found in adult 4-week-old inbred strains of mice. High incidence of spontaneous myocarditis was found in aged 8-week-old DBA/2 mice, and low incidence was in 8-week-old BALB/c or C57BL/6 mice. The lesions, limited to the right ventricle, were most severe in DBA/2 mice. TRX was upregulated, and the expression was correlated with the severity of the disease in these strains. Also, 8-hydroxy-2′-deoxyguanosine (8-OHdG), which was an established marker for oxidative stress, was concomitantly positive in necrotic lesions among them. In addition, the long-term anti-oxidant treatment with N-acetylcysteine (NAC) suppressed the development of spontaneous myocarditis. Thus, TRX may be induced by the spontaneously developed myocarditis, and the redox-regulating system may play an important role in the development of aging-related myocarditis.