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http://dx.doi.org/10.5352/JLS.2008.18.11.1513

4-Hydroxynonenal Induces Endothelial Apoptosis through Mitochondrial Depolarization  

Kang, Dae-Yeon (College of Pharmacy, Pusan National University)
Lee, Ji-Young (College of Pharmacy, Pusan National University)
Kim, Min-Sun (College of Pharmacy, Pusan National University)
Kim, Chul-Hong (College of Pharmacy, Pusan National University)
Kim, Hyung-Keun (College of Pharmacy, Pusan National University)
Lee, Sun-Mi (College of Pharmacy, Pusan National University)
Kwon, Young-Mi (College of Pharmacy, Pusan National University)
Lee, Jae-won (College of Pharmacy, Pusan National University)
Baik, Hyung-Suk (Genetic Engineering Research Institute, Pusan National University)
Yu, Byung-Pal (4Department of Physiology, The University of Texas Health Science)
Chung, Hae-Young (College of Pharmacy, Pusan National University)
Publication Information
Journal of Life Science / v.18, no.11, 2008 , pp. 1513-1520 More about this Journal
Abstract
The 4-Hydroxynonenal (HNE) affects vascular dysfunctions probably through the interruption of the cellular redox balance. To better understand vascular abnormalities resulting from the accumulation of HNE, we delineated mechanism by which mitochondrial apoptosis occurs in the YPEN-1 endothelial cells. HNE treatment led to the loss of mitochondrial membrane potential (${\delta}{\Psi}_m$), resulting in the release of cytochrome c. Data showed decreased Bcl-2 and increased Bax protein levels in HNE-treated cells. NAC, a reactive oxygen species (ROS) scavenger, and penicillamine, the peroxynitrite scavenger, blocked HNE-mediated ROS generation, thereby thwarting the cytochrome c release and apoptosis. The treatment of the cells with zVAD-fmk, a broad range caspase inhibitor did not suppress HNE-induced apoptosis, suggesting that the apoptosis might be the possibility of caspase-independent process. Our findings delineate the underlying mechanism of the HNE induced endothelial apoptosis by triggering depolarization of mitochondria membrane potential that can lead to the deterioration of vasculature homeostasis and subsequent vascular dysfunction with aging.
Keywords
4-Hydroxynonenal; apoptosis; mitochondrial membrane potential; caspase-3; cytochrome C release;
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1 Naumann, U., J. Wischhusen, S. Weit, J. Rieger, H. Wolburg, U. Massing and M. Weller. 2004. Alkylphosphocholine-induced glioma cell death is BCL-X(L)-sensitive, caspase-independent and characterized by massive cytoplasmic vacuole formation. Cell Death Differ. 11, 1326-1341.   DOI   ScienceOn
2 Muradian, K. and D. O. Schachtschabel. 2001. The role of apoptosis in aging and age-related disease: update, Z. Gerontol. Geriatr. 34, 441-446.   DOI   ScienceOn
3 Zamzami, N., P. M. Marchetti, C. Castedo, J. L. Zanin, P. Vayssiere, X. Petit and G. Kroemer. 1995. Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J. Exp. Med. 181, 1661-16672.   DOI   ScienceOn
4 Cheng, J. Z., S. S. Singhal, A. Sharma, M. Saini, Y. Yang, S. Awasthi, P. Zimniak and Y. C. Awasthi. 2001. Transfection of mGSTA4 in HL-60 cells protects against 4-hydroxynonenal-induced apoptosis by inhibiting JNK-mediated signaling. Arch. Biochem. Biophys. 392, 197-207.   DOI   ScienceOn
5 Toyokuni, S., K. Uchida, K. Okamoto, Y. Hattori-Nakakuki, H. Hiai and E. R. Stadtman. 1994. Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate. Proc. Natl. Acad. Sci. 91, 2616-2620.   DOI   ScienceOn
6 Lee, J. Y., J. H. Je, D. H. Kim, S. W. Chung, Y. Zou, N. D. Kim, M. A. Yoo, H. S. Baik, B. P. Yu and H. Y. Chung. 2004. Induction of endothelial apoptosis by 4-hydroxyhexenal. Eur. J. Biochem. 271, 1339-1347.   DOI   ScienceOn
7 Kruman, P., M, Castedo, S. A, Susin, N, Zamzami, T. Hirsch, A. Macho, A. Haeffner, F. Hirsch, M. Geuskens and G. Kroemer. 1996. Mitochondrial permeability transition is a central coordinating event of apoptosis. J. Exp. Med. 184, 1155-1160   DOI   ScienceOn
8 Uchida, K. 2000. Role of reactive aldehyde in cardiovascular diseases. Free Radic. Biol. Med. 28, 1685-1696.   DOI   ScienceOn
9 Yang, J., X. Liu, K. Bhalla, C. N. Kim, A. M. Ibrado, J. Cai, T. I. Peng, D. P. Jones and X. Wang. 1997. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129-1132.   DOI   ScienceOn
10 West, J. D., C. Ji and L. J. Marnett. 2005. Modulation of DNA fragmentation factor 40 nuclease activity by poly (ADP-ribose) polymerase-1. J. Biol. Chem. 280, 15141-15147.   DOI   ScienceOn
11 Wang, D. S., N. Iwata, E. Hama, T. C. Saido and D. W. Dickson. 2003. Oxidized neprilysin in aging and Alzheimer's disease brains. Biochem. Biophys. Res. Commun. 310, 236-241.   DOI   ScienceOn
12 Habib, A., C. Creminon, Y. Frobert, J. Grassi, P. Pradelles and J. Maclouf. Demonstration of an inducible cyclooxygenase in human endothelial cells using antibodies raised against the carboxyl-terminal region of the cyclooxygenase-2. J. Biol. Chem. 268, 23448-23454.
13 Uchida, K. 2003. 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog. Lipid Res. 42, 318-343.   DOI   ScienceOn
14 Usatyuk, P. V. and V. Natarajan. 2004. Role of mitogen-activated protein kinases in 4-hydroxy-2-nonenal-induced actin remodeling and barrier function in endothelial cells. J. Biol. Chem. 279, 11789-11797.   DOI   ScienceOn
15 Pollack, R., F. Marcheselli, F. Moroni and C. Pieri. 2002. Apoptosis in human aortic endothelial cells induced by hyperglycemic condition involves mitochondrial depolarization and is prevented by N-acetyl-L-cysteine. Metabolism 51, 1384-1388.   DOI   ScienceOn
16 Haynes, R. L., B. Brune and A. J. Townsend. 2001. Apoptosis in RAW 264.7 cells exposed to 4-hydroxy-2-nonenal: dependence on cytochrome C release but not p53 accumulation. Free Radic. Biol. Med. 30, 884-894.   DOI   ScienceOn
17 Hamilton Jr., R. F., L. Li, W.L. Eschenbacher, L. Szweda and A. Holian. 1998. Potential involvement of 4-hydroxynonenal in the response of human lung cells to ozone. Am. J. Physiol. 274, 8-16.
18 Esterbauer, H., R. J. Schaur and H. Zollner. 1991. Chemistry and biochemistry of 4-hydroxynenenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med. 11, 81-128.   DOI   ScienceOn
19 Donovan, M. and T. Cotter. 2004. Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death. Biochim. Biophy. Acta. 1644, 133-147.   DOI   ScienceOn
20 Compton, C. N., A. P. Franko, M. T. Murray, L. N. Diebel and S. A. Dulchavsky. 1998. Signaling of apoptotic lung injury by lipid hydroperoxides. J. Trauma. 44, 783-788.   DOI   ScienceOn
21 Colquhoun, A. and R. I. Schumacher. 2001. N-Linolenic acid and eicosapentaenoic acid induce modifications in mitochondrial metabolism, reactive oxygen species generation, lipid peroxidation and apoptosis in Walker 256 rat carcinosarcoma cells. Biochim. Biophys. Acta. 1533, 207-219.   DOI   ScienceOn
22 Chiarpotto, E., F. Biasi, A. Scavazza, S. Camandola, M. U. Dianzani and G. Poli. 1995. Metabolism of 4-hydroxy-2-nonenal and aging. Bioche. Biophys. Res. Commun. 207, 477-484.   DOI   ScienceOn
23 Arita, K., H. Kobuchi, T. Utsumi, Y. Takehara, J. Akiyama, A. A. Horton and K. Utsumi. 2001. Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids. Biochem. Pharmacol. 62, 821-828.   DOI   ScienceOn
24 Mikhailov, V., M. Mikhailova, D. J. Pulkrabek, Z. Dong, M. A. Venkatachalam and P. Saikumar. 2001. Bcl-2 prevents Bax oligomerization in the mitochondrial outer membrane. J. Biol. Chem. 276, 18361-18374.   DOI   ScienceOn
25 Cathcart, R., E. Schwiers and B. N. Ames. 1983. Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein fluorescent assay. Anal. Biochem. 134, 111-116.   DOI   ScienceOn
26 Bursztajn, S., J. J. Feng, S. A. Berman and A. Nanda. 2000. Poly (ADP-ribose) polymerase induction is an early signal of apoptosis in human neuroblastoma. Brain Res. Mol. Brain Res. 76, 363-376.   DOI   ScienceOn
27 Anuradha, C. D., S. Kanno and S. Hirano. 2001. Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells. Free Radic. Biol. Med. 31, 367-373.   DOI   ScienceOn
28 Ali, S. F., C. P. LeBel and S. C. Bondy. 1992. Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13, 637-648.
29 Pryor, W. A., R. Cueto, X. Jin, W. H. Koppenol, M. Ngu-Schwemlein, G. L. Squadrito, P. L. Uppu and R. M. Uppu. 1995. A practical method for preparing peroxynitrite solutions of low ionic strength and free of hydrogen peroxide. Free Radic. Biol. Med. 18, 75-83.   DOI   ScienceOn
30 Meng, J., N. Sakata, S. Takebayashi, T. Asano, T. Futata, R. Nagai, K. Ikeda, S. Horiuchi, T. Myint and N. Taniguchi. 1998. Glycoxidation in aortic collagen from STZ-induced diabetic rats and its relevance to vascular damage. Atherosclerosis 136, 355-365.   DOI   ScienceOn
31 Pollack, M. and C. Leeuwenburgh. 2001. Apoptosis and aging: role of the mitochondria. J. Gerontol. Biol. Sci. Med. Sci. 56, 475-482.   DOI
32 Joza, N., S. A, Susin, E. Daugas, W. L. Stanford, S. K. Cho, C. Y. Li, T. Sasaki, A. J. Elia, H. Y. Cheng, L. Ravagnan, K. F. Ferri, N. Zamzami, A. Wakeham, R. Hakem, H. Yoshida, Y. Y. Kong, T. W. Mak, J. C. Zuniga-Pflucker, G. Kroemer and J. M. Penninger. 2001. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 410, 549-554.   DOI   ScienceOn
33 Kruman, I. I. and M. P. Mattson. 1999. Pivotal role of mitochondrial calcium uptake in neural cell apoptosis and necrosis. J. Neurochem. 72, 529-540.   DOI   ScienceOn
34 Kang, Y. H., M. J. Yi, M. J. Kim, M. T. Park, S. Bae, C. M. Kang, C. K. Cho, I. C. Park, M. J. Park, C. H. Rhee, S. I. Hong, H. Y. Chung, Y. S. Lee and S. J. Lee. 2004. Caspase-independent cell death by arsenic trioxide in human cervical cancer cells: reactive oxygen species-mediated poly (ADP-ribose) polymerase-1 activation signals apoptosis-inducing factor release from mitochondria. Cancer Res. 64, 8960-8967.   DOI   ScienceOn
35 Pollack, B. S., B. K. Park and B. P. Yu. 1996. 4-Hydroxyhexenal is a potent induces of the mitochondrial permeability transition. J. Biol. Chem. 271, 6033-6038.   DOI
36 Pollack, J. J., H. Bertrand and B. P. Yu. 1995. Inhibition of adenine nucleotide translocator by lipid peroxidation products. Free Radic. Biol. Med. 19, 583-590   DOI   ScienceOn
37 Oltvai, Z. N., C. L. Milliman and S. J. Korsmeyer. Bcl-2 heterodimerizes in vivo with a conserved homologue, Bax that accelerates programmed cell death. 2003. Cell 74, 609-619.
38 Ruef, J., M. Moser, C. Bode, W. Kubler and M. S. Runge. 2001. 4-Hydroxynonenal induces apoptosis, NF-$_KB$-activation and formation of 8-isoprostane in vascular smooth muscle cells. Basic Res. Cardiol. 96, 143-150.   DOI
39 Yu, B. P. and H. Y. Chung. 2001. Oxidative stress and vascular aging, Diabetes Res. Clin. Pract. 2, 73-80.   DOI   ScienceOn
40 Cathcart, A. G., V. Borutaite and G. C. Brown. 1999. Superoxide dismutase and hydrogen peroxide cause rapid nitric oxide breakdown, peroxynitrite production and subsequent cell death. Biochim. Biophys. Acta. 1454, 275-288.   DOI   ScienceOn
41 Schonfeld, P. and R. Bohnensack. 1997. Fatty acid-promoted mitochondrial permeability transition by membrane depolarization and binding to the ADP/ATP carrier. FEBS Lett. 420, 167-170.   DOI   ScienceOn