Archives of Toxicology

, Volume 86, Issue 4, pp 633–642 | Cite as

Diesel exhaust particulate extracts inhibit transcription of nuclear respiratory factor-1 and cell viability in human umbilical vein endothelial cells

Molecular Toxicology

Abstract

Endothelial dysfunction precedes cardiovascular disease and is accompanied by mitochondrial dysfunction. Here we tested the hypothesis that diesel exhaust particulate extracts (DEPEs), prepared from a truck run at different speeds and engine loads, would inhibit genomic estrogen receptor activation of nuclear respiratory factor-1 (NRF-1) transcription in human umbilical vein endothelial cells (HUVECs). Additionally, we examined how DEPEs affect NRF-1-regulated TFAM expression and, in turn, Tfam-regulated mtDNA-encoded cytochrome c oxidase subunit I (COI, MTCO1) and NADH dehydrogenase subunit I (NDI) expression as well as cell proliferation and viability. We report that 17β-estradiol (E2), 4-hydroxytamoxifen (4-OHT), and raloxifene increased NRF-1 transcription in HUVECs in an ER-dependent manner. DEPEs inhibited NRF-1 transcription, and this suppression was not ablated by concomitant treatment with E2, 4-OHT, or raloxifene, indicating that the effect was not due to inhibition of ER activity. While E2 increased HUVEC proliferation and viability, DEPEs inhibited viability but not proliferation. Resveratrol increased NRF-1 transcription in an ER-dependent manner in HUVECs, and ablated DEPE inhibition of basal NRF-1 expression. Given that NRF-1 is a key nuclear transcription factor regulating genes involved in mitochondrial activity and biogenesis, these data suggest that DEPEs may adversely affect mitochondrial function leading to endothelial dysfunction and resveratrol may block these effects.

Keywords

Endothelial cells Diesel exhaust Diesel exhaust particles NRF-1, Mitochondrial activity, Resveratrol 

Notes

Acknowledgments

This project was supported by NIH R01 DK53220 to C.M.K. and American Heart Association pre-doctoral fellowship 315087B to K.A.M. We thank Dr. Ryoichi Kizu for the DEPEs used in this study. We thank Dr. Barbara J. Clark for her suggestions for this manuscript.

References

  1. Andersson H, Piras E, Demma J, Hellman B, Brittebo E (2009) Low levels of the air pollutant 1-nitropyrene induce DNA damage, increased levels of reactive oxygen species and endoplasmic reticulum stress in human endothelial cells. Toxicology 262:57–64PubMedCrossRefGoogle Scholar
  2. Anenberg SC, Horowitz LW, Tong DQ, West JJ (2010) An estimate of the global burden of anthropogenic ozone and fine particulate matter on premature human mortality using atmospheric modeling. Environ Health Perspect 118:1189–1195PubMedCrossRefGoogle Scholar
  3. Arnal JF, Fontaine C, Billon-Gales A, Favre J, Laurell H, Lenfant F, Gourdy P (2010) Estrogen receptors and endothelium. Arterioscler Thromb Vasc Biol 30:1506–1512PubMedCrossRefGoogle Scholar
  4. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM (2000) Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 141:3657–3667PubMedCrossRefGoogle Scholar
  5. Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC Jr, Tager I (2004) Air pollution and cardiovascular disease: a statement for healthcare professionals from the expert panel on population and prevention science of the American heart association. Circulation 109:2655–2671PubMedCrossRefGoogle Scholar
  6. Chambliss KL, Yuhanna IS, Anderson RG, Mendelsohn ME, Shaul PW (2002) ERbeta has nongenomic action in caveolae. Mol Endocrinol 16:938–946PubMedCrossRefGoogle Scholar
  7. Chao M-W, Kozlosky J, Po IP, Strickland PO, Svoboda KKH, Cooper K, Laumbach RJ, Gordon MK (2011) Diesel exhaust particle exposure causes redistribution of endothelial tube VE-cadherin. Toxicology 279:73–84PubMedCrossRefGoogle Scholar
  8. Davidson SM, Duchen MR (2007) Endothelial mitochondria: contributing to vascular function and disease. Circ Res 100:1128–1141PubMedCrossRefGoogle Scholar
  9. Duckles SP, Krause DN (2011) Mechanisms of cerebrovascular protection: estrogen, inflammation and mitochondria. Acta Physiol (Oxf) 203:149–154Google Scholar
  10. Guo Y, Tong S, Zhang Y, Barnett AG, Jia Y, Pan X (2010) The relationship between particulate air pollution and emergency hospital visits for hypertension in Beijing, China. Sci Total Environ 408:4446–4450PubMedCrossRefGoogle Scholar
  11. Huo L, Scarpulla RC (2001) Mitochondrial DNA instability and peri-implantation lethality associated with targeted disruption of nuclear respiratory factor 1 in mice. Mol Cell Biol 21:644–654PubMedCrossRefGoogle Scholar
  12. Ivanova MM, Luken KH, Zimmer AS, Lenzo FL, Smith RJ, Arteel MW, Kollenberg TJ, Mattingly KA, Klinge CM (2011) Tamoxifen increases nuclear respiratory factor 1 transcription by activating estrogen receptor β and AP-1 recruitment to adjacent promoter binding sites. FASEB J 25:1402–1416PubMedCrossRefGoogle Scholar
  13. Iwanari M, Nakajima M, Kizu R, Hayakawa K, Yokoi T (2002) Induction of CYP1A1, CYP1A2, and CYP1B1 mRNAs by nitropolycyclic aromatic hydrocarbons in various human tissue-derived cells: chemical-, cytochrome P450 isoform-, and cell-specific differences. Arch Toxicol 76:287–298PubMedCrossRefGoogle Scholar
  14. Kawasaki S, Takizawa H, Takami K, Desaki M, Okazaki H, Kasama T, Kobayashi K, Yamamoto K, Nakahara K, Tanaka M, Sagai M, Ohtoshi T (2001) Benzene-extracted components are important for the major activity of diesel exhaust particles: effect on interleukin-8 gene expression in human bronchial epithelial cells. Am J Respir Cell Mol Biol 24:419–426PubMedGoogle Scholar
  15. Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18:357–368PubMedCrossRefGoogle Scholar
  16. Kizu R, Okamura K, Toriba A, Mizokami A, Burnstein KL, Klinge CM, Hayakawa K (2003) Antiandrogenic activities of diesel exhaust particle extracts in PC3/AR human prostate carcinoma cells. Toxicol Sci 76:299–309PubMedCrossRefGoogle Scholar
  17. Kizu R, Otsuki N, Kishida Y, Toriba A, Mizokami A, Burnstein KL, Klinge CM, Hayakawa K (2004) A new luciferase reporter gene assay for the detection of androgenic and antiandrogenic effects based on a human prostate specific antigen promoter and PC3/AR human prostate cancer cells. Anal Sci 20:55–59PubMedCrossRefGoogle Scholar
  18. Klein GP, Hodge EM, Diamond ML, Yip A, Dann T, Stern G, Denison MS, Harper PA (2006) Gas-phase ambient air contaminants exhibit significant dioxin-like and estrogen-like activity in vitro. Environ Health Perspect 114:697–703PubMedCrossRefGoogle Scholar
  19. Klinge CM, Blankenship KA, Risinger KE, Bhatnagar S, Noisin EL, Sumanasekera WK, Brey DM, Keynton RS (2005) Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem 280:7460–7468PubMedCrossRefGoogle Scholar
  20. Klinge CM, Wickramasinghe NS, Ivanova MM, Dougherty SM (2008) Resveratrol stimulates nitric oxide production by increasing estrogen receptor {alpha}-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J 22:2185–2197PubMedCrossRefGoogle Scholar
  21. Kodavanti UP, Thomas R, Ledbetter AD, Schladweiler MC, Shannahan JH, Wallenborn JG, Lund AK, Campen MJ, Butler EO, Gottipolu RR, Nyska A, Richards JE, Andrews D, Jaskot RH, McKee J, Kotha SR, Patel RB, Parianandi NL (2011) Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles. Environ Health Perspect 119:312–318Google Scholar
  22. Landvik NE, Gorria M, Arlt VM, Asare N, Solhaug A, Lagadic-Gossmann D, Holme JA (2007) Effects of nitrated-polycyclic aromatic hydrocarbons and diesel exhaust particle extracts on cell signalling related to apoptosis: possible implications for their mutagenic and carcinogenic effects. Toxicology 231:159–174PubMedCrossRefGoogle Scholar
  23. Levy JI, Buonocore JJ, von Stackelberg K (2010) Evaluation of the public health impacts of traffic congestion: a health risk assessment. Environ Health 9:65PubMedCrossRefGoogle Scholar
  24. Li C-H, Cheng Y-W, Hsu Y-T, Hsu Y-J, Liao P-L, Kang J-J (2010a) Benzo[a]pyrene inhibits angiogenic factors-induced αvβ3 integrin expression, neovasculogenesis and angiogenesis in human umbilical vein endothelial cells. Toxicol Sci 118:544–553Google Scholar
  25. Li R, Ning Z, Cui J, Yu F, Sioutas C, Hsiai T (2010b) Diesel exhaust particles modulate vascular endothelial cell permeability: implication of ZO-1 expression. Toxicol Lett 197:163–168PubMedCrossRefGoogle Scholar
  26. Mattingly KA, Ivanova MM, Riggs KA, Wickramasinghe NS, Barch MJ, Klinge CM (2008) Estradiol stimulates transcription of nuclear respiratory factor-1 and increases mitochondrial biogenesis. Mol Endocrinol 22:609–622PubMedCrossRefGoogle Scholar
  27. Meyers MJ, Sun J, Carlson KE, Marriner GA, Katzenellenbogen BS, Katzenellenbogen JA (2001) Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J Med Chem 44:4230–4251PubMedCrossRefGoogle Scholar
  28. Miller VM, Duckles SP (2008) Vascular actions of estrogens: functional implications. Pharmacol Rev 60:210–241PubMedCrossRefGoogle Scholar
  29. Monforton C (2006) Weight of the evidence or wait for the evidence? Protecting underground miners from diesel particulate matter. Am J Public Health 96:271–276PubMedCrossRefGoogle Scholar
  30. Montiel M, de la Blanca EP, Jimenez E (2006) P2Y receptors activate MAPK/ERK through a pathway involving PI3 K/PDK1/PKC-zeta in human vein endothelial cells. Cell Physiol Biochem 18:123–134PubMedCrossRefGoogle Scholar
  31. Okamura K, Kizu R, Toriba A, Klinge CM, Hayakawa K (2002) Antiestrogenic activity of extracts of diesel exhaust particulate matter in MCF-7 human breast carcinoma cells. Polycycl Aromat Compd 22:747–759CrossRefGoogle Scholar
  32. Okamura K, Kizu R, Hayakawa K, Toriba A, Mizokami A, Burnstein KL, Klinge CM, Kato S (2004a) Variation in the antiandrogenic activity of diesel exhaust particulates emitted under different engine loads. Polycycl Aromat Compd 24:743–757CrossRefGoogle Scholar
  33. Okamura K, Kizu R, Toriba A, Murahashi T, Mizokami A, Burnstein KL, Klinge CM, Hayakawa K (2004b) Antiandrogenic activity of extracts of diesel exhaust particles emitted from diesel-engine truck under different engine loads and speeds. Toxicology 195:243–254PubMedCrossRefGoogle Scholar
  34. Perera F (1981) Carcinogenicity of airborne fine particulate benzo(a)pyrene: an appraisal of the evidence and the need for control. Environ Health Perspect 42:163–185PubMedCrossRefGoogle Scholar
  35. Razmara A, Sunday L, Stirone C, Wang XB, Krause DN, Duckles SP, Procaccio V (2008) Mitochondrial effects of estrogen are mediated by estrogen receptor alpha in brain endothelial cells. J Pharmacol Exp Ther 325:782–790PubMedCrossRefGoogle Scholar
  36. Rocha M, Apostolova N, Hernandez-Mijares A, Herance R, Victor VM (2010) Oxidative stress and endothelial dysfunction in cardiovascular disease: mitochondria-targeted therapeutics. Curr Med Chem 17:3827–3841PubMedCrossRefGoogle Scholar
  37. Rouse RL, Murphy G, Boudreaux MJ, Paulsen DB, Penn AL (2008) Soot nanoparticles promote biotransformation, oxidative stress, and inflammation in murine lungs. Am J Respir Cell Mol Biol 39:198–207PubMedCrossRefGoogle Scholar
  38. Scarpulla RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576:1–14PubMedGoogle Scholar
  39. Scarpulla RC (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97:673–683PubMedCrossRefGoogle Scholar
  40. Scarpulla RC (2008) Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann N Y Acad Sci 1147:321–334PubMedCrossRefGoogle Scholar
  41. Simkhovich BZ, Kleinman MT, Kloner RA (2008) Air pollution and cardiovascular injury: epidemiology, toxicology, and mechanisms. J Am Coll Cardiol 52:719–726PubMedCrossRefGoogle Scholar
  42. Stauffer SR, Coletta CJ, Tedesco R, Nishiguchi G, Carlson K, Sun J, Katzenellenbogen BS, Katzenellenbogen JA (2000) Pyrazole ligands: structure–affinity/activity relationships and estrogen receptor-alpha-selective agonists. J Med Chem 43:4934–4947PubMedCrossRefGoogle Scholar
  43. Stirone C, Duckles SP, Krause DN, Procaccio V (2005) Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Mol Pharmacol 68:959–965PubMedCrossRefGoogle Scholar
  44. Sumanasekera WK, Zhao L, Ivanova M, Morgan DD, Noisin EL, Keynton RS, Klinge CM (2006) Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cells. Cell Tissue Res 324:243–253PubMedCrossRefGoogle Scholar
  45. Sumanasekera WK, Ivanova MM, Johnston BJ, Dougherty SM, Sumanasekera GU, Myers SR, Ali Y, Kizu R, Klinge CM (2007a) Rapid effects of diesel exhaust particulate extracts on intracellular signaling in human endothelial cells. Toxicol Lett 174:61–73PubMedCrossRefGoogle Scholar
  46. Sumanasekera WK, Sumanasekera GU, Mattingly KA, Dougherty SM, Keynton RS, Klinge CM (2007b) Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activity. Am J Physiol Cell Ph 293:C566–C573CrossRefGoogle Scholar
  47. Sun J, Huang YR, Harrington WR, Sheng S, Katzenellenbogen JA, Katzenellenbogen BS (2002) Antagonists selective for estrogen receptor alpha. Endocrinology 143:941–947PubMedCrossRefGoogle Scholar
  48. Tabas I (2010) The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res 107:839–850PubMedCrossRefGoogle Scholar
  49. Wijayaratne AL, McDonnell DP (2001) The human estrogen receptor-alpha is a ubiquitinated protein whose stability is affected differentially by agonists, antagonists, and selective estrogen receptor modulators. J Biol Chem 276:35684–35692PubMedCrossRefGoogle Scholar
  50. Wijayaratne AL, Nagel SC, Paige LA, Christensen DJ, Norris JD, Fowlkes DM, McDonnell DP (1999) Comparative analyses of mechanistic differences among antiestrogens. Endocrinology 140:5828–5840PubMedCrossRefGoogle Scholar
  51. Yamazaki H, Hatanaka N, Kizu R, Hayakawa K, Shimada N, Guengerich FP, Nakajima M, Yokoi T (2000) Bioactivation of diesel exhaust particle extracts and their major nitrated polycyclic aromatic hydrocarbon components, 1-nitropyrene and dinitropyrenes, by human cytochromes P450 1A1, 1A2, and 1B1. Mutat Res 472:129–138PubMedGoogle Scholar
  52. Zhao H, Ma JK, Barger MW, Mercer RR, Millecchia L, Schwegler-Berry D, Castranova V, Ma JY (2009) Reactive oxygen species- and nitric oxide-mediated lung inflammation and mitochondrial dysfunction in wild-type and iNOS-deficient mice exposed to diesel exhaust particles. J Toxicol Environ Health A 72:560–570PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular MedicineUniversity of Louisville School of MedicineLouisvilleUSA

Personalised recommendations