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比较 Hypoxia(缺氧)和 Hyperoxia(富氧)诱导的 Pleurodeles waltl 和 Mus musculus 肺部表观遗传表达模式的改变。

Comparison of hypoxia- and hyperoxia-induced alteration of epigene expression pattern in lungs of Pleurodeles waltl and Mus musculus.

机构信息

Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.

Department of Stem Cell Biology, Atomic Bomb Diseases Institute, Nagasaki University, Sakamoto, Nagasaki, Japan.

出版信息

PLoS One. 2024 Feb 28;19(2):e0299661. doi: 10.1371/journal.pone.0299661. eCollection 2024.

Abstract

Epigenetics is an emerging field of research because of its involvement in susceptibility to diseases and aging. Hypoxia and hyperoxia are known to be involved widely in various pathophysiologies. Here, we compared the differential epigene expression pattern between Pleurodeles waltl and Mus musculus (commonly known as Iberian ribbed newt and mouse, respectively) exposed to hypoxia and hyperoxia. Adult healthy newts and mice were exposed to normobaric hypoxia (8% O2) and hyperoxia (80% O2) for 2 hours. We collected the lungs and analyzed the expression of hypoxia-inducible factor 1 alpha (Hif1α) and several key epigenes from DNA methyltransferase (DNMT) family, histone deacetylase (HDAC) family, and methyl-CpG binding domain (MBD) family. The exposure to hypoxia significantly increased the mRNA levels of DNA methyltransferase 3 alpha (Dnmt3α), methyl-CpG binding domain protein 2 (Mbd2), Mbd3, and histone deacetylase 2 (Hdac2) in lungs of newts, but decreased the mRNA levels of DNA methyltransferase 1 (Dnmt1) and Dnmt3α in lungs of mice. The exposure to hyperoxia did not significantly change the expression of any gene in either newts or mice. The differential epigene expression pattern in response to hypoxia between newts and mice may provide novel insights into the prevention and treatment of disorders developed due to hypoxia exposure.

摘要

表观遗传学是一个新兴的研究领域,因为它涉及疾病易感性和衰老。缺氧和高氧已被广泛认为参与各种病理生理过程。在这里,我们比较了缺氧和高氧暴露下的欧洲蝾螈( Pleurodeles waltl )和小鼠( Mus musculus ,通常称为伊比利亚肋突螈和小鼠)之间差异的表观基因表达模式。成年健康的蝾螈和小鼠分别暴露于常压缺氧(8% O2 )和高氧(80% O2 )中 2 小时。我们收集了肺部并分析了缺氧诱导因子 1α(Hif1α)和几个关键的表观基因,包括 DNA 甲基转移酶(DNMT)家族、组蛋白去乙酰化酶(HDAC)家族和甲基-CpG 结合域(MBD)家族的表达。缺氧暴露显著增加了蝾螈肺部中 DNA 甲基转移酶 3α(Dnmt3α)、甲基-CpG 结合域蛋白 2(Mbd2)、Mbd3 和组蛋白去乙酰化酶 2(Hdac2)的 mRNA 水平,但降低了小鼠肺部中 DNA 甲基转移酶 1(Dnmt1)和 Dnmt3α的 mRNA 水平。高氧暴露并未显著改变蝾螈或小鼠任何基因的表达。蝾螈和小鼠对缺氧的差异表观基因表达模式可能为预防和治疗因缺氧暴露而导致的疾病提供新的思路。

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