Perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in non-human primates.
Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility. Similarly, molecular studies in mice have shown that in utero exposure to cardiovascular disease (CVD) risk factors such as environmental tobacco smoke (ETS) increased adult atherogenic susceptibility and mitochondrial damage; however, the molecular effects of similar exposures in primates are not yet known. To determine whether perinatal ETS exposure increased mitochondrial damage, dysfunction and oxidant stress in primates, archived tissues from the non-human primate model Macaca mulatta (M. mulatta) were utilized. M. mulatta were exposed to low levels of ETS (1 mg/m(3) total suspended particulates) from gestation (day 40) to early childhood (1 year), and aortic tissues were assessed for oxidized proteins (protein carbonyls), antioxidant activity (SOD), mitochondrial function (cytochrome oxidase), and mitochondrial damage (mitochondrial DNA damage). Results revealed that perinatal ETS exposure resulted in significantly increased oxidative stress, mitochondrial dysfunction and damage which were accompanied by significantly decreased mitochondrial antioxidant capacity and mitochondrial copy number in vascular tissue. Increased mitochondrial damage was also detected in buffy coat tissues in exposed M. mulatta. These studies suggest that perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in primates, potentially increasing adult disease susceptibility.
Westbrook
David G
DG
Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, VH G019F, 1530 3rd Avenue S., Birmingham, AL 35294-0019, USA.
Anderson
Peter G
PG
Pinkerton
Kent E
KE
Ballinger
Scott W
SW
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D015153:Blotting, Western; D004247:DNA / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D008253:Macaca mulatta; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D004247:DNA; D003576:Electron Transport Complex IV; D013482:Superoxide Dismutase; D014028:Tobacco Smoke Pollution; D014443:Tyrosine; D000099156:Superoxide Dismutase 2; C002744:3-nitrotyrosine