The emerging role of the thioredoxin system in angiogenesis.
Although there have been a multitude of studies, the mechanisms of angiogenesis remain incompletely understood. Increasing evidence suggests that cellular redox homeostasis is an important regulator of angiogenesis. The thioredoxin (TRX) system functions as an endogenous antioxidant that can exert influence over endothelial cell function via modulation of cellular redox status. It has become apparent that the cytosolic TRX1 isoform participates in both canonical and novel angiogenic signaling pathways and may represent an avenue for therapeutic exploitation. Recent studies have further identified a role for the mitochondrial isoform TRX2 in ischemia-induced angiogenesis. TRX-interacting protein (TXNIP) is the endogenous inhibitor of TRX redox activity that has been implicated in growth factor-mediated angiogenesis. As TXNIP is strongly induced by glucose, this molecule could be of consequence to disordered angiogenesis manifest in diabetes mellitus. This review will focus on data implicating the TRX system in endothelial cell homeostasis and angiogenesis.
Dunn
Louise L
LL
Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, New South Wales, Australia. mkcng@med.usyd.edu.au
Buckle
Andrew M
AM
Cooke
John P
JP
Ng
Martin K C
MK
D000975:Antioxidants / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010084:Oxidation-Reduction; D013879:Thioredoxins / Q000502:physiology*
D000975:Antioxidants; D002352:Carrier Proteins; C486715:TXNIP protein, human; D013879:Thioredoxins
Mol Cell Biol. 2000 Jan;20(1):402-15
10594042
Lab Invest. 2005 Jun;85(6):798-807
15834431
Oncogene. 2004 Nov 25;23(55):8868-75
15480426
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8
9108029
Proc Natl Acad Sci U S A. 1987 Feb;84(3):804-8
3027706
Cancer Res. 2005 Jun 1;65(11):4485-9
15930262
Cancer Res. 1996 Dec 15;56(24):5765-70
8971189
Biochem Soc Trans. 2008 Oct;36(Pt 5):963-5
18793170
Oncogene. 2005 Apr 28;24(19):3110-20
15735682
Int J Cancer. 2005 Mar 10;114(1):139-43
15523699
Free Radic Biol Med. 2001 Jun 1;30(11):1191-212
11368918
Mol Cell Biol. 1996 Sep;16(9):4604-13
8756616
Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2666-72
17023680
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4131-6
10097175
J Biol Chem. 2009 Sep 11;284(37):24996-5003
19605364
J Biol Chem. 2002 Jul 19;277(29):26496-500
12011048
Nat Cell Biol. 2002 Oct;4(10):743-9
12244325
Mol Cell Biol. 2005 Mar;25(5):1980-8
15713651
Diabetes. 1999 Oct;48(10):1899-906
10512352
Carcinogenesis. 2009 Nov;30(11):1865-71
19773351
Am J Pathol. 2007 Mar;170(3):1108-20
17322393
Biochem J. 2006 Feb 15;394(Pt 1):207-16
16209660
Hypertension. 2009 Aug;54(2):338-44
19506101
Atheroscler Suppl. 2003 Dec;4(4):53-60
14664903
Int J Cancer. 2001 May 20;95(3):198-204
11307155
FASEB J. 2006 Jan;20(1):121-3
16254043
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3921-6
18322014
Cancer Res. 2001 Oct 1;61(19):7333-8
11585774
J Biol Chem. 2008 Jan 25;283(4):2397-406
17998203
Hum Pathol. 2008 Feb;39(2):201-8
17949784
EMBO J. 1998 May 1;17(9):2596-606
9564042
J Med Chem. 2009 Feb 12;52(3):763-70
19123857
J Lab Clin Med. 2003 Jul;142(1):46-51
12878985
Circulation. 2002 Sep 10;106(11):1403-9
12221060
Cancer Res. 2002 Sep 1;62(17):5089-95
12208766
Biochim Biophys Acta. 2009 Oct;1790(10):1191-7
19595745
Antioxid Redox Signal. 2007 Jan;9(1):25-47
17115886
EMBO J. 1992 Sep;11(9):3323-35
1380454
Nutr Cancer. 2004;50(2):221-31
15623470
EMBO J. 1992 Feb;11(2):653-65
1537340
Semin Thromb Hemost. 2000;26(5):503-11
11129406
FEBS Lett. 2003 Sep 11;551(1-3):153-8
12965221
Mol Cell Biol. 2003 Feb;23(3):916-22
12529397
Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):495-502
19150880
Biochem Biophys Res Commun. 2005 Oct 28;336(3):770-8
16143294
Mutat Res. 1995 Feb;316(3):103-22
7862174
Dev Biol. 1996 Aug 25;178(1):179-85
8812119
J Biol Chem. 1999 Jul 30;274(31):21645-50
10419473
J Nutr. 2004 Jun;134(6):1475-80
15173414
Mol Cancer Ther. 2003 Mar;2(3):235-43
12657718
Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):106-12
17082486
Circ Res. 2002 Jun 28;90(12):1259-66
12089063
Endocrinology. 2005 May;146(5):2397-405
15705778
Arch Physiol Biochem. 2006 Oct-Dec;112(4-5):189-218
17178593
Free Radic Biol Med. 2007 Mar 15;42(6):872-81
17320769
J Biol Chem. 2005 Nov 25;280(47):39394-402
16172122
J Clin Invest. 1987 May;79(5):1440-6
3106416
J Immunol. 2000 Jun 15;164(12):6287-95
10843682
J Clin Invest. 2005 Mar;115(3):733-8
15696199
Biochem Biophys Res Commun. 2000 May 19;271(3):796-800
10814541
Pharmazie. 2006 Mar;61(3):223-9
16599264
J Biol Chem. 1964 Oct;239:3436-44
14245400
J Clin Invest. 2008 Dec;118(12):3904-16
19033661
FASEB J. 2001 Sep;15(11):1877-85
11532967
J Biol Chem. 1999 Sep 24;274(39):27891-7
10488136
Int J Oncol. 2008 Feb;32(2):377-85
18202760
Nature. 1999 Sep 2;401(6748):86-90
10485711
J Biol Chem. 2006 Aug 4;281(31):21884-21891
16766796
Mol Carcinog. 1999 Dec;26(4):213-25
10569799
Biochem Biophys Res Commun. 2009 Apr 17;381(4):660-5
19254690
J Biol Chem. 2004 Sep 3;279(36):37559-65
15234975
J Biol Chem. 2010 Feb 5;285(6):3997-4005
19959470
Mol Cancer Ther. 2006 Mar;5(3):630-6
16546977
Br J Cancer. 2005 Jan 31;92(2):350-8
15655539
J Biol Chem. 2004 Jun 4;279(23):24387-93
15047687
Nucleic Acids Res. 1992 Aug 11;20(15):3821-30
1508666
J Mol Cell Cardiol. 2005 Nov;39(5):813-22
16198371
Diabetes. 2008 Apr;57(4):938-44
18171713
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11700-5
12189205
J Biol Chem. 1998 Mar 13;273(11):6297-302
9497357
Free Radic Biol Med. 2008 Jan 1;44(1):91-8
18045551
Clin Cancer Res. 2001 Oct;7(10):3087-91
11595699
J Neurooncol. 2006 Apr;77(2):131-40
16292483
Nature. 1999 Sep 2;401(6748):82-5
10485710
Mol Cell Biol. 2004 Nov;24(21):9414-23
15485910
Circulation. 2010 Mar 16;121(10):1244-55
20194885
J Biol Chem. 2004 Jul 16;279(29):30369-74
15128745
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15540-5
17030815
Anticancer Res. 2002 Nov-Dec;22(6C):4045-8
12553030
J Biol Chem. 2007 Mar 9;282(10):7482-90
17220299
Oncogene. 2006 Jun 15;25(25):3528-36
16607285
Circ Res. 2007 Dec 7;101(12):1328-38
17916779
J Lab Clin Med. 2006 Feb;147(2):83-90
16459166
Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1877-83
15976330
Int J Oncol. 2005 Apr;26(4):1049-52
15754001
Am J Physiol Endocrinol Metab. 2009 May;296(5):E1133-9
19258488
FEBS Lett. 2004 Nov 19;577(3):427-33
15556622
Circ Res. 2002 Oct 18;91(8):689-95
12386145
Exp Eye Res. 2007 Aug;85(2):270-9
17603038
Nature. 1992 Oct 29;359(6398):843-5
1279431
J Clin Invest. 1997 Jun 1;99(11):2625-34
9169492
Cancer Res. 2003 Jan 15;63(2):432-40
12543799
Cardiovasc Res. 1994 Aug;28(8):1176-9
7525061
Chem Biol Interact. 1998 Apr 24;111-112:23-34
9679540
Biochem Biophys Res Commun. 1967 Nov 17;29(3):264-8
4864797
Endocrinology. 2002 Sep;143(9):3695-8
12193586
J Reprod Fertil. 1991 Nov;93(2):525-39
1787474
Cancer Res. 2007 Nov 15;67(22):10823-30
18006827
Biochem Biophys Res Commun. 2008 Aug 8;372(4):880-5
18541147
J Clin Invest. 2003 Jun;111(12):1933-43
12813029
Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):77-83
17068286
Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8104-9
9223322
BMC Cancer. 2007 Jun 07;7:96
17555594
J Biol Chem. 2004 Jun 25;279(26):27302-14
15082714