Functional and gene expression analysis of hTERT overexpressed endothelial cells.
Telomerase dysfunction contributes to cellular senescence. Recent advances indicate the importance of senescence in maintaining vascular cell function in vitro. Human telomerase reverse transcriptase (hTERT) overexpression is thought to lead to resistance to apoptosis and oxidative stress. However, the mechanism in endothelial lineage cells is unclear. We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro. High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture. Also, angiogenic responses were observed in hTERT over-expressed endothelial cell. These cells showed a delay in senescence and appeared more resistant to stressed conditions. PI3K/Akt-related gene levels were enhanced in hTERT overexpressed endothelial cells. An up-regulated PI3K/Akt pathway caused by hTERT overexpression might contribute to anti-apoptosis and survival effects in endothelial lineage cells.
Takano
Haruna
H
Institute of Biomedical Research and Innovation, Kobe, Japan;
Murasawa
Satoshi
S
Asahara
Takayuki
T
J Biol Chem. 1999 Sep 10;274(37):26141-8
10473565
J Clin Invest. 2000 Aug;106(4):493-9
10953024
Oncogene. 1998 Feb 19;16(7):825-32
9484773
Biochem Biophys Res Commun. 2004 Sep 3;321(4):788-94
15358096
Mol Cell Biol. 1998 Apr;18(4):2143-52
9528786
Circ Res. 2004 Apr 2;94(6):768-75
14963003
Nature. 1990 Aug 30;346(6287):866-8
2392154
Science. 1997 Jan 31;275(5300):665-8
9005852
Regul Pept. 2000 Jul 28;91(1-3):21-7
10967199
Am J Pathol. 2004 Jul;165(1):11-24
15215158
J Biol Chem. 2005 Apr 15;280(15):14790-8
15687494
Cell. 1999 Jul 23;98(2):147-57
10428027
J Biol Chem. 1998 Nov 13;273(46):30336-43
9804796
Nature. 1990 May 31;345(6274):458-60
2342578
Circ Res. 2003 May 16;92(9):1049-55
12676819
J Cell Sci. 2004 May 1;117(Pt 11):2417-26
15126641
J Biol Chem. 2002 Mar 15;277(11):9036-42
11781308
Nature. 2000 Nov 23;408(6811):492-5
11100733
Nature. 1998 Nov 5;396(6706):84-8
9817205
Nat Med. 2000 Sep;6(9):1004-10
10973320
Circ Res. 2000 Jan 7-21;86(1):24-9
10625301
Science. 1998 Jan 16;279(5349):349-52
9454332
Bioessays. 1990 Aug;12(8):363-9
2241933
Circulation. 2002 Aug 27;106(9):1133-9
12196341
J Biol Chem. 2000 Mar 31;275(13):9102-5
10734041
J Neurosci. 1998 Apr 15;18(8):2933-43
9526010
Mol Cell Biol. 1998 Jul;18(7):4131-40
9632797
Nat Genet. 1999 Jan;21(1):115-8
9916803
Exp Gerontol. 1992 Jul-Aug;27(4):383-9
1333985
Nat Genet. 1999 Jan;21(1):111-4
9916802
Angiogenesis. 2002;5(1-2):21-33
12549857
Science. 1997 Aug 15;277(5328):955-9
9252327
Cell Cycle. 2004 Jun;3(6):811-6
15118409