Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model.
Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model.
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DOI：
10.1186/1471-2199-7-27
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发表时间：
2006-09-11
影响因子：
--
通讯作者：
Au DW
中科院分区：
文献类型：
--
作者：
Yu RM;Chen EX;Kong RY;Ng PK;Mok HO;Au DW
目前对缺氧、缺氧诱导因子-1（HIF-1）和端粒酶逆转录酶（TERT）基因表达之间关系的认识主要基于人类癌细胞的体外研究。虽然有几个报告表明，缺氧条件下HIF-1介导的人类TERT基因的上调，也有相互矛盾的结果。到目前为止，还不确定这些发现是否可以直接外推到其他整个动物系统的非肿瘤组织中。虽然鱼类经常遇到环境缺氧，但鱼类非肿瘤组织中缺氧对TERT的体内调节几乎仍然未知。本研究以成年青鳉为模式鱼。我们已经克隆并鉴定了一个3261 bp的全长TERT cDNA，omTERT，它编码一个1086个氨基酸的蛋白质。它包含在其他脊椎动物TERT中保守的所有功能基序。基序E是最高度保守的，在鱼类TERT中显示90.9-100%的总体同一性，在脊椎动物中显示63.6%的总体同一性。对omTERT基因的5 '侧翼序列的分析鉴定了两个HRE（缺氧反应元件; nt. - 283和-892）核心。瞬时转染实验表明HIF-1α的过表达诱导了omTERT启动子的活性。omTERT基因在常氧条件下在鱼类中普遍表达，尽管表达水平不同，其中在性腺中观察到最高表达，在肝脏中观察到最低表达。在体内，睾丸和肝脏中的omTERT表达在缺氧反应中（分别在96 h和48 h）显著上调，其中还观察到omHIF-1α和促红细胞生成素（omEpo）基因的伴随诱导。原位杂交分析表明，缺氧诱导omTERTmRNA在肝尾侧区的肝细胞和睾丸中含有精原细胞的囊肿中是明显的。这项研究首次证明了在整个鱼类系统中体内缺氧调节TERT表达。我们的研究结果支持了缺氧通过omHIF-1在体内非肿瘤性鱼类肝脏和睾丸中上调omTERT表达的观点。总体而言，TERT基因的结构和调控在从鱼类到人类的脊椎动物中高度保守。
Current understanding on the relationships between hypoxia, hypoxia-inducible factor-1 (HIF-1) and telomerase reverse transcriptase (TERT) gene expression are largely based on in vitro studies in human cancer cells. Although several reports demonstrated HIF-1- mediated upregulation of the human TERT gene under hypoxia, conflicting findings have also been reported. Thus far, it remains uncertain whether these findings can be directly extrapolated to non-tumor tissues in other whole animal systems in vivo. While fish often encounter environmental hypoxia, the in vivo regulation of TERT by hypoxia in non-neoplastic tissues of fish remains virtually unknown. The adult marine medaka (Oryzias melastigma) was employed as a model fish in this study. We have cloned and characterized a 3261-bp full-length TERT cDNA, omTERT, which encodes a protein of 1086 amino acids. It contains all of the functional motifs that are conserved in other vertebrate TERTs. Motif E is the most highly conserved showing 90.9–100% overall identity among the fish TERTs and 63.6% overall identity among vertebrates. Analysis of the 5'-flanking sequence of the omTERT gene identified two HRE (hypoxia-responsive element; nt. – 283 and – 892) cores. Overexpression of the HIF-1α induced omTERT promoter activity as demonstrated using transient transfection assays. The omTERT gene is ubiquitously expressed in fish under normoxia, albeit at varying levels, where highest expression was observed in gonads and the lowest in liver. In vivo expression of omTERT was significantly upregulated in testis and liver in response to hypoxia (at 96 h and 48 h, respectively), where concomitant induction of the omHIF-1α and erythropoietin (omEpo) genes was also observed. In situ hybridization analysis showed that hypoxic induction of omTERT mRNA was clearly evident in hepatocytes in the caudal region of liver and in spermatogonia-containing cysts in testis. This study demonstrates for the first time, hypoxic regulation of TERT expression in vivo in a whole fish system. Our findings support the notion that hypoxia upregulates omTERT expression via omHIF-1 in non-neoplastic fish liver and testis in vivo. Overall, the structure and regulation of the TERT gene is highly conserved in vertebrates from fish to human.
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影响因子：
3.6
作者：
Achi, MV;Ravindranath, N;Dym, M
通讯作者：
Dym, M
影响因子：
8
作者：
Anderson, CJ;Hoare, SF;Keith, WN
通讯作者：
Keith, WN
DOI：
10.1073/pnas.93.18.9493
发表时间：
1996-09-03
影响因子：
11.1
作者：
Hochachka, PW;Buck, LT;Land, SC
通讯作者：
Land, SC
影响因子：
5.3
作者：
Nishi, H;Nakada, T;Isaka, K
通讯作者：
Isaka, K
影响因子：
5.3
作者：
Kajimura, S;Aida, K;Duan, CM
通讯作者：
Duan, CM