PMID- 16961934
OWN - NLM
STAT- MEDLINE
DCOM- 20061017
LR  - 20181113
IS  - 1471-2199 (Electronic)
IS  - 1471-2199 (Linking)
VI  - 7
DP  - 2006 Sep 11
TI  - Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in 
      non-tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model.
PG  - 27
AB  - BACKGROUND: 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. RESULTS: 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-1alpha 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-1alpha 
      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. CONCLUSION: 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.
FAU - Yu, Richard M K
AU  - Yu RM
AD  - Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee 
      Avenue, Kowloon, Hong Kong. bhrichyu@cityu.edu.hk
FAU - Chen, Eric X H
AU  - Chen EX
FAU - Kong, Richard Y C
AU  - Kong RY
FAU - Ng, Patrick K S
AU  - Ng PK
FAU - Mok, Helen O L
AU  - Mok HO
FAU - Au, Doris W T
AU  - Au DW
LA  - eng
SI  - GENBANK/DQ286654
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060911
PL  - England
TA  - BMC Mol Biol
JT  - BMC molecular biology
JID - 100966983
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Eye Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Muscle Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/*biosynthesis/genetics
MH  - Enzyme Induction
MH  - Eye Proteins/genetics
MH  - Female
MH  - Humans
MH  - Hypoxia/*enzymology/genetics
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - In Situ Hybridization
MH  - Liver/enzymology
MH  - Male
MH  - Molecular Sequence Data
MH  - Muscle Proteins/genetics
MH  - Oryzias/genetics/*metabolism
MH  - Oxidative Stress
MH  - Recombinant Fusion Proteins/biosynthesis/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Species Specificity
MH  - Spermatozoa/enzymology
MH  - Telomerase/*biosynthesis/genetics
MH  - Testis/enzymology
MH  - Transcriptional Activation
MH  - Vertebrates/genetics
MH  - Viscera/enzymology
PMC - PMC1578579
EDAT- 2006/09/12 09:00
MHDA- 2006/10/18 09:00
PMCR- 2006/09/11
CRDT- 2006/09/12 09:00
PHST- 2006/06/06 00:00 [received]
PHST- 2006/09/11 00:00 [accepted]
PHST- 2006/09/12 09:00 [pubmed]
PHST- 2006/10/18 09:00 [medline]
PHST- 2006/09/12 09:00 [entrez]
PHST- 2006/09/11 00:00 [pmc-release]
AID - 1471-2199-7-27 [pii]
AID - 10.1186/1471-2199-7-27 [doi]
PST - epublish
SO  - BMC Mol Biol. 2006 Sep 11;7:27. doi: 10.1186/1471-2199-7-27.