Regulation of platelet granule exocytosis by S-nitrosylation.
Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and alpha-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis.
Morrell
Craig N
CN
Department of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Matsushita
Kenji
K
Chiles
Kelly
K
Scharpf
Robert B
RB
Yamakuchi
Munekazu
M
Mason
Rebecca J A
RJ
Bergmeier
Wolfgang
W
Mankowski
Joseph L
JL
Baldwin
William M
WM
Faraday
Nauder
N
Lowenstein
Charles J
CJ
D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D006152:Cyclic GMP / Q000502:physiology; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005089:Exocytosis; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins / Q000502:physiology
D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP
Biochem Biophys Res Commun. 2000 Jan 27;267(3):875-80
10673384
Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1480-5
8643658
Blood. 2000 Nov 15;96(10):3334-42
11071625
Biochem Biophys Res Commun. 2000 Dec 20;279(2):412-9
11118301
J Biol Chem. 2001 Jun 22;276(25):21991-4
11301340
Circ Res. 2001 Apr 27;88(8):756-62
11325866
Thromb Haemost. 2001 Jul;86(1):214-21
11487009
Blood. 2002 Aug 1;100(3):1081-3
12130530
Cell. 2003 Jan 10;112(1):77-86
12526795
Trends Pharmacol Sci. 2003 Feb;24(2):91-5
12559774
Cell. 2003 Feb 21;112(4):519-33
12600315
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H637-42
12750066
Cell. 2003 Oct 17;115(2):139-50
14567912
Circ Res. 2003 Nov 14;93(10):907-16
14615494
J Clin Invest. 2003 Nov;112(10):1589-96
14617760
Cell. 2003 Dec 26;115(7):851-62
14697203
J Exp Med. 2004 Feb 2;199(3):347-56
14744991
Blood. 1981 May;57(5):946-55
6111365
Lancet. 1987 Nov 7;2(8567):1057-8
2889967
Biochem Biophys Res Commun. 1987 Nov 13;148(3):1482-9
2825688
Naunyn Schmiedebergs Arch Pharmacol. 1987 Nov;336(5):566-71
2830546
Proc Natl Acad Sci U S A. 1988 Nov;85(21):7852-6
3186695
FASEB J. 1989 Jan;3(1):31-6
2642868
FASEB J. 1989 Jul;3(9):2007-18
2545495
Pharm Res. 1989 Aug;6(8):651-9
2510139
Arch Biochem Biophys. 1990 Jun;279(2):286-90
2112369
Pharmacol Toxicol. 1990 Jul;67(1):1-7
1975691
J Biol Chem. 1990 Nov 5;265(31):19028-34
2172242
Biofactors. 1990 Oct;2(4):219-25
2282138
Pharmacol Rev. 1991 Jun;43(2):109-42
1852778
Blood. 1991 Aug 15;78(4):1033-40
1868238
J Cell Biochem. 1991 May;46(1):27-36
1874796
Br J Clin Pharmacol. 1992;34 Suppl 1:29S-35S
1633076
Am J Cardiol. 1992 Sep 24;70(8):18B-22B
1529922
Science. 1992 Dec 18;258(5090):1898-902
1281928
J Biol Chem. 1993 Feb 5;268(4):2662-6
8428942
Blood Rev. 1993 Mar;7(1):52-62
8467233
Am J Cardiol. 1993 Sep 9;72(8):33C-38C
7690516
Adv Exp Med Biol. 1993;344:251-64
7516113
J Cell Biol. 1994 Aug;126(4):945-54
8051214
Cell. 1994 Sep 23;78(6):931-6
7923362
Am J Physiol. 1996 May;270(5 Pt 2):H1640-8
8928869
Biochem Biophys Res Commun. 1996 May 24;222(3):780-5
8651922
J Clin Invest. 1997 Nov 1;100(9):2146-52
9410890
Circulation. 1998 Jan 27;97(3):263-7
9462528
Br J Pharmacol. 1998 May;124(1):141-8
9630353
Biochemistry (Mosc). 1998 Jul;63(7):794-801
9721331
J Biol Chem. 1999 Jan 22;274(4):2492-501
9891020
FEBS Lett. 1999 Jan 15;442(2-3):162-6
9928994
J Biol Chem. 1999 May 14;274(20):14368-75
10318860
Circ Res. 1999 Jun 25;84(12):1416-21
10381894
Blood. 1999 Aug 15;94(4):1313-8
10438719
Biosci Rep. 1999 Apr;19(2):51-71
10888468
Nature. 1994 Nov 3;372(6501):55-63
7969419
Adv Pharmacol. 1995;34:263-75
8562439
Cell. 1993 Nov 5;75(3):409-18
8221884