O-GlcNAcylation: a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension.
O-Linked attachment of beta-N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Preliminary data show that O-GlcNAcylation may represent a key regulatory mechanism in the vasculature, modulating contractile and relaxant responses. Proteins with an important role in vascular function, such as endothelial nitric oxide synthase, sarcoplasmic reticulum Ca(2+)-ATPase, protein kinase C, mitogen-activated protein kinases, and proteins involved in cytoskeleton regulation and microtubule assembly are targets for O-GlcNAcylation, indicating that this posttranslational modification may play an important role in vascular reactivity. Here, we will focus on a few specific pathways that contribute to vascular function and cardiovascular disease-associated vascular dysfunction, and the implications of their modification by O-GlcNAc. New chemical tools have been developed to detect and study O-GlcNAcylation, including inhibitors of O-GlcNAc enzymes, chemoenzymatic tagging methods, and quantitative proteomics strategies; these will also be briefly addressed. An exciting challenge in the future will be to better understand the cellular dynamics of this posttranslational modification, as well as the signaling pathways and mechanisms by which O-GlcNAc is regulated on specific proteins in the vasculature in health and disease.
Lima
Victor V
VV
Department of Physiology, Medical College of Georgia, Augusta, GA, USA; Department of Pharmacology, University of Sao Paulo, Sao Paulo, SP, Brazil.
Rigsby
Christiné S
CS
Hardy
David M
DM
Webb
R Clinton
RC
Tostes
Rita C
RC
Mol Cell Proteomics. 2007 Aug;6(8):1365-79
17507370
Eur J Biochem. 1999 Jun;262(3):824-31
10411645
Adv Exp Med Biol. 1995;376:115-23
8597237
Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E1-E8
16339923
Ann N Y Acad Sci. 2002 Jun;967:102-11
12079840
Cardiovasc Res. 2007 Jan 15;73(2):288-97
16970929
Circulation. 2002 Jul 23;106(4):466-72
12135947
Science. 2001 Mar 23;291(5512):2376-8
11269319
J Pharmacol Exp Ther. 2008 Dec;327(3):602-9
18768779
Methods Mol Biol. 2004;284:175-94
15173616
J Biol Chem. 2004 May 14;279(20):20636-42
15014073
Mol Cell Proteomics. 2006 May;5(5):923-34
16452088
Biochem Biophys Res Commun. 2006 Feb 10;340(2):526-34
16376298
Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):651-7
18174452
J Biol Chem. 2002 Jun 7;277(23):20833-9
11916963
J Am Chem Soc. 2003 Dec 31;125(52):16162-3
14692737
Circulation. 2008 Mar 4;117(9):1172-82
18285568
J Immunol. 2001 Apr 15;166(8):5155-60
11290798
Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2227-36
17208994
Biochem Biophys Res Commun. 2003 Mar 14;302(3):435-41
12615051
Methods Mol Biol. 2009;534:251-79
19277546
Biochim Biophys Acta. 1999 Dec 6;1473(1):161-71
10580136
Nat Chem Biol. 2008 Feb;4(2):97-106
18202679
Sci STKE. 2005 Nov 29;2005(312):re13
16317114
Endocrinology. 2006 Jan;147(1):222-31
16365142
J Am Chem Soc. 2007 Dec 5;129(48):14854-5
17994748
J Biol Chem. 2004 Jul 16;279(29):30133-42
15138254
Methods Mol Biol. 2009;464:227-54
18951188
Biochim Biophys Acta. 2006 May-Jun;1761(5-6):599-617
16781888
J Proteome Res. 2009 May;8(5):2608-14
19284785
J Am Chem Soc. 2006 Dec 27;128(51):16484-5
17177381
Nat Struct Mol Biol. 2004 Oct;11(10):1001-7
15361863
J Am Chem Soc. 2006 Apr 5;128(13):4234-5
16568991
Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H335-42
18469144
J Am Chem Soc. 2004 Sep 1;126(34):10500-1
15327282
Chem Biol. 2008 Aug 25;15(8):799-807
18721751
Nat Chem Biol. 2007 Jun;3(6):339-48
17496889
Cell Mol Life Sci. 2003 Feb;60(2):222-8
12678487
Annu Rev Biochem. 1989;58:841-74
2673024
Diabetes. 2002 Apr;51(4):1146-56
11916938
J Biol Chem. 2004 Oct 29;279(44):45759-65
15322139
Physiol Res. 2001;50(6):537-46
11829314
Org Lett. 2007 Jun 7;9(12):2321-4
17508759
J Biol Chem. 2005 Apr 15;280(15):14579-85
15703172
J Biochem Mol Biol. 2007 Nov 30;40(6):1058-68
18047804
Shock. 2006 Jun;25(6):600-7
16721268
J Biol Chem. 1991 Mar 15;266(8):4706-12
2002019
Exp Physiol. 2005 Jul;90(4):449-55
15890798
Med Mol Morphol. 2005 Jun;38(2):84-91
15944815
Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H515-23
19098112
Nature. 2001 Dec 13;414(6865):813-20
11742414
Biochem Pharmacol. 2005 Nov 25;70(11):1537-47
16139252
Am J Physiol Endocrinol Metab. 2003 Sep;285(3):E584-91
12900380
Clin Exp Pharmacol Physiol. 2007 Oct;34(10):972-8
17714081
J Biol Chem. 2005 Jul 8;280(27):25313-22
15795231
J Biol Chem. 2004 Dec 17;279(51):53665-73
15485860
Diabetes. 1986 Oct;35(10):1163-73
3530846
Life Sci. 2007 Feb 20;80(11):1051-6
17174344
Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E974-80
18728220
J Clin Invest. 2001 Nov;108(9):1341-8
11696579
J Biol Chem. 1992 May 5;267(13):9005-13
1533623
Chem Commun (Camb). 2006 Nov 13;(42):4372-4
17057847
Diabetes. 1999 Aug;48(8):1562-71
10426374
Mol Cell Proteomics. 2004 Jun;3(6):577-85
14985449
Mol Biol Cell. 2008 Oct;19(10):4130-40
18653473
Adv Physiol Educ. 2003 Dec;27(1-4):201-6
14627618
J Biol Chem. 2002 May 24;277(21):19229-35
11904304
Biochemistry. 2001 Jul 3;40(26):7845-52
11425311
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10695-9
12136128
J Biol Chem. 2008 Dec 5;283(49):33935-41
18840611
Glycobiology. 2006 May;16(5):415-21
16434389
J Am Soc Hypertens. 2008 Nov-Dec;2(6):410-7
19884969
Curr Opin Struct Biol. 2003 Oct;13(5):631-6
14568619
J Proteome Res. 2005 May-Jun;4(3):950-7
15952742
Mol Biosyst. 2007 Nov;3(11):766-72
17940659
Biochim Biophys Acta. 2010 Feb;1800(2):107-21
19664691
Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13132-7
15340146
Trends Endocrinol Metab. 2008 Dec;19(10):380-9
18929495
J Mol Cell Cardiol. 2007 Jan;42(1):177-85
17069847
Osteoarthritis Cartilage. 2003 Apr;11(4):290-8
12681956
J Biol Chem. 2003 Feb 14;278(7):5399-409
12435728
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12222-6
11050244
J Am Chem Soc. 2006 Nov 22;128(46):14768-9
17105262
Nature. 2007 Apr 26;446(7139):1017-22
17460662
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11870-5
16085713
J Am Chem Soc. 2005 Oct 26;127(42):14588-9
16231908
Invest Ophthalmol Vis Sci. 2006 Feb;47(2):664-72
16431966
J Biol Chem. 1992 Aug 25;267(24):16911-21
1512232
FEBS Lett. 2002 Jan 16;510(3):166-70
11801247
Mol Cell Biol. 2004 Feb;24(4):1680-90
14749383
J Cell Biochem. 2005 Oct 15;96(3):579-88
16052526
Methods Enzymol. 1994;230:443-60
8139512
Methods Enzymol. 2005;405:139-71
16413314
J Biol Chem. 2008 Aug 1;283(31):21411-7
18519567
J Neurosci Res. 1995 Jun 1;41(2):270-8
7650762
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5313-8
11959983
J Biol Chem. 2008 May 9;283(19):13009-20
18353774
J Biol Chem. 2002 Jan 18;277(3):1755-61
11788610
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9528-33
15210983
FEBS Lett. 2003 Jul 3;546(1):154-8
12829252
Hypertension. 2009 Feb;53(2):166-74
19139380
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11952-7
16882729
Endocrinology. 1997 Jun;138(6):2501-7
9165041
Metab Syndr Relat Disord. 2008 Sep;6(3):159-70
18699719
Prog Nucleic Acid Res Mol Biol. 2003;73:107-36
12882516
J Leukoc Biol. 2002 Apr;71(4):632-40
11927650
Biochim Biophys Acta. 2008 May;1783(5):695-712
18295358
Biochem Biophys Res Commun. 2001 May 11;283(3):634-40
11341771
Biochim Biophys Acta. 2005 Apr 15;1743(3):305-15
15843043
Clin Sci (Lond). 2007 Jun;112(7):375-84
17324119
Am J Physiol Heart Circ Physiol. 2009 Jan;296(1):H13-28
19028792
Am J Med Sci. 2000 Mar;319(3):138-42
10746823
J Biol Chem. 1999 Nov 5;274(45):32015-22
10542233
J Clin Invest. 1996 Aug 15;98(4):930-6
8770864
Diabetologia. 2001 Jun;44(6):674-92
11440360
Biochem Biophys Res Commun. 2007 Sep 21;361(2):414-20
17645866
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2820-5
10717000
Biochem Biophys Res Commun. 2006 Dec 1;350(4):1038-43
17045574
Mol Cell Proteomics. 2002 Oct;1(10):791-804
12438562
J Biol Chem. 2000 Apr 14;275(15):10983-8
10753899
Biochim Biophys Acta. 2004 Jul 6;1673(1-2):13-28
15238246
J Biol Chem. 2004 Sep 10;279(37):38466-70
15247246
Vascul Pharmacol. 2005 Jun;43(1):19-29
15955745
Anal Bioanal Chem. 2008 Apr;390(8):2089-97
18369606
Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8894-9
19458039
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9116-21
12874386
Circ Res. 2003 Nov 28;93(11):1047-58
14645135
Shock. 2008 Apr;29(4):431-40
17909453
Diabetes. 1999 May;48(5):1101-7
10331416
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5735-9
10801981