Suppression of Apoptosis by Nitric Oxide via Inhibition of Interleukin-1β–converting Enzyme (ICE)-like and Cysteine Protease Protein (CPP)-32–like Proteases

Journal of Experimental Medicine - Tập 185 Số 4 - Trang 601-608 - 1997
Stefanie Dimmeler1, Judith Haendeler1, Michael Nehls1, Andreas M. Zeiher1
1From the Molecular Cardiology Group, Department of Internal Medicine IV, University of Frankfurt, Germany

Tóm tắt

Physiological levels of shear stress alter the genetic programm of cultured endothelial cells and are associated with reduced cellular turnover rates and formation of atherosclerotic lesions in vivo. To test the hypothesis that shear stress (15 dynes/cm2) interferes with programmed cell death, apoptosis was induced in human umbilical venous cells (HUVEC) by tumor necrosis factor-α (TNF-α). Apoptosis was quantified by ELISA specific for histone-associated DNA-fragments and confirmed by demonstrating the specific pattern of internucleosomal DNA-fragmentation. TNF-α (300 U/ml) mediated increase of DNA-fragmentation was completely abrogated by shear stress (446 ± 121% versus 57 ± 11%, P <0.05). This anti-apoptotic activity of shear stress decreased after pharmacological inhibition of endogenous nitric oxide (NO)-synthase by NG-monomethyl-l-arginine and was completely reproduced by exogenous NO-donors. The activation of interleukin-1β–converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like cysteine proteases was required to mediate TNF-α–induced apoptosis of HUVEC. Endothelial-derived nitric oxide (NO) as well as exogenous NO donors inhibited TNF-α–induced cysteine protease activation. Inhibition of CPP-32 enzyme activity was due to specific S-nitrosylation of Cys 163, a functionally essential amino acid conserved among ICE/CPP-32–like proteases. Thus, we propose that shear stress-mediated NO formation interferes with cell death signal transduction and may contribute to endothelial cell integrity by inhibition of apoptosis.

Từ khóa


Tài liệu tham khảo

Ku, 1985, Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress, Arteriosclerosis, 5, 293, 10.1161/01.ATV.5.3.293

Caplan, 1973, Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta, Atherosclerosis, 17, 401, 10.1016/0021-9150(73)90031-2

Cohen, 1993, Apoptosis, Immunol Today, 14, 126, 10.1016/0167-5699(93)90214-6

Steller, 1995, Mechanisms and genes of cellular suicide, Science (Wash DC), 267, 1445, 10.1126/science.7878463

Kumar, 1995, ICE-like proteases in apoptosis, Trends Biochem Sci, 20, 198, 10.1016/S0968-0004(00)89007-6

Thornberry, 1992, A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes, Nature (Lond), 356, 768, 10.1038/356768a0

Robaye, 1991, Tumor necrosis factor induces apoptosis (programmed cell death) in normal endothelial cells in vitro, Am J Pathol, 138, 447

Malek, 1994, Molecular aspects of signal transduction of shear stress in the endothelial cell, J Hypertens, 12, 989, 10.1097/00004872-199409000-00001

Azumi, 1994, Mechanism of deletion of endothelial cells during regression of the corpus luteum, Lab Invest, 51, 206

Kohler, 1991, Increased blood flow inhibits neointimal hyperplasia in endothelialized vascular grafts, Circ Res, 69, 1557, 10.1161/01.RES.69.6.1557

Nerem, 1993, Hemodynamics and vascular endothelial biology, J Cardiovasc Pharmacol, 21, S6, 10.1097/00005344-199321001-00002

Noris, 1995, Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions, Circ Res, 76, 536, 10.1161/01.RES.76.4.536

Rösl, 1992, A simple and rapid method for detection of apoptosis in human cells, Nucleic Acids Res, 20, 5243, 10.1093/nar/20.19.5243

Dimmeler, 1995, Endotoxin-induced changes of endothelial cell viability and permeability: protective effect of a 21-aminosteroid, Eur J Pharmacol, 287, 257, 10.1016/0014-2999(95)00499-8

Bump, 1995, Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35, Science (Wash DC), 269, 1885, 10.1126/science.7569933

Thornberry, 1994, Interleukin-1 beta converting enzyme, Methods Enzymol, 244, 615, 10.1016/0076-6879(94)44045-X

Enari, 1996, Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis, Nature (Lond), 380, 723, 10.1038/380723a0

Ramage, 1995, Expression, refolding, and autocatalytic proteolytic processing of the interleukin-1 beta-converting enzyme precursor, J Biol Chem, 270, 9378, 10.1074/jbc.270.16.9378

Molina y Vedia, 1992, Nitric oxideinduced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation, J Biol Chem, 267, 24929, 10.1016/S0021-9258(19)73985-4

Stamler, 1992, S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme, Proc Natl Acad Sci USA, 89, 8087, 10.1073/pnas.89.17.8087

Uematsu, 1995, Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress, Am J Physiol, 269, C1371, 10.1152/ajpcell.1995.269.6.C1371

Messmer, 1994, p53 expression in nitric oxide-induced apoptosis, FEBS Lett, 355, 23, 10.1016/0014-5793(94)01161-3

Nicholson, 1995, Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis, Nature (Lond), 376, 37, 10.1038/376037a0

Stamler, 1992, S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds, Proc Natl Acad Sci USA, 89, 444, 10.1073/pnas.89.1.444

Stamler, 1995, S-nitrosothiols and the bioregulatory actions of nitrogen oxides through reactions with thiol groups, Curr Top Microbiol Immunol, 196, 19

Dimmeler, 1992, Nitric oxide causes ADP-ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase, J Biol Chem, 267, 16771, 10.1016/S0021-9258(18)41847-9

Mannick, 1994, Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation, Cell, 79, 1137, 10.1016/0092-8674(94)90005-1

Genaro, 1995, Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels, J Clin Invest, 95, 1884, 10.1172/JCI117869

Nathan, 1992, Nitric oxide as a secretory product of mammalian cells, FASEB J, 6, 3051, 10.1096/fasebj.6.12.1381691

Thông tin
Thông tin xuất bản

Journal of Experimental Medicine

Tập 185 Số 4

601-608

Thông tin tác giả