A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

被引:123
作者
Brette, Fabien [1 ,5 ]
Shiels, Holly A. [2 ,5 ]
Galli, Gina L. J. [2 ]
Cros, Caroline [1 ,5 ]
Incardona, John P. [3 ]
Scholz, Nathaniel L. [3 ]
Block, Barbara A. [1 ,4 ]
机构
[1] Stanford Univ, Hopkins Marine Stn, Dept Biol, Pacific Grove, CA 93950 USA
[2] Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester M13 9NT, Lancs, England
[3] NOAA, Northwest Fisheries Sci Ctr, Seattle, WA 98112 USA
[4] Stanford Univ, Hopkins Marine Stn, Tuna Res & Conservat Ctr, Pacific Grove, CA 93950 USA
[5] Univ Bordeaux, INSERM U1045, LIRYC Inst Rythmol & Modelisat Cardiaque, Campus Xavier Arnozan PTIB, F-33600 Pessac, France
关键词
POLYCYCLIC AROMATIC-HYDROCARBONS; WEATHERED CRUDE-OIL; FISH EMBRYOS; DEVELOPMENTAL TOXICITY; CARDIAC-ARRHYTHMIA; ZEBRAFISH; EXPOSURE; SENSITIVITY; CHANNELS; ABNORMALITIES;
D O I
10.1038/srep41476
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.
引用
收藏
页数:9
相关论文
共 54 条
[1]   Heart malformation is an early response to TCDD in embryonic zebrafish [J].
Antkiewicz, DS ;
Burns, CG ;
Carney, SA ;
Peterson, RE ;
Heideman, W .
TOXICOLOGICAL SCIENCES, 2005, 84 (02) :368-377
[2]   Zebrafish model for human long QT syndrome [J].
Arnaout, Rima ;
Ferrer, Tania ;
Huisken, Jan ;
Spitzer, Kenneth ;
Stainier, Didier Y. R. ;
Tristani-Firouzi, Martin ;
Chi, Neil C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (27) :11316-11321
[3]  
Bers D., 2001, Excitation-Contraction Coupling and Cardiac Contractile Force, VVolume 237
[4]   Cardiac excitation-contraction coupling [J].
Bers, DM .
NATURE, 2002, 415 (6868) :198-205
[5]   Temperature effects on metabolic rate of juvenile Pacific bluefin tuna Thunnus orientalis [J].
Blank, Jason M. ;
Morrissette, Jeffery M. ;
Farwell, Charles J. ;
Price, Matthew ;
Schallert, Robert J. ;
Block, Barbara A. .
JOURNAL OF EXPERIMENTAL BIOLOGY, 2007, 210 (23) :4254-4261
[6]   Quantification of calcium entry at the T-tubules and surface membrane in rat ventricular myocytes [J].
Brette, F ;
Sallé, L ;
Orchard, CH .
BIOPHYSICAL JOURNAL, 2006, 90 (01) :381-389
[7]   Crude Oil Impairs Cardiac Excitation-Contraction Coupling in Fish [J].
Brette, Fabien ;
Machado, Ben ;
Cros, Caroline ;
Incardona, John P. ;
Scholz, Nathaniel L. ;
Block, Barbara A. .
SCIENCE, 2014, 343 (6172) :772-776
[8]   THE CONTROL OF CALCIUM-RELEASE IN HEART-MUSCLE [J].
CANNELL, MB ;
CHENG, H ;
LEDERER, WJ .
SCIENCE, 1995, 268 (5213) :1045-1049
[9]   Sensitivity of fish embryos to weathered crude oil:: Part I.: Low-level exposure during incubation causes malformations, genetic damage, and mortality in larval Pacific herring (Clupea pallasi) [J].
Carls, MG ;
Rice, SD ;
Hose, JE .
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 1999, 18 (03) :481-493
[10]   CALCIUM SPARKS - ELEMENTARY EVENTS UNDERLYING EXCITATION-CONTRACTION COUPLING IN HEART-MUSCLE [J].
CHENG, H ;
LEDERER, WJ ;
CANNELL, MB .
SCIENCE, 1993, 262 (5134) :740-744