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Perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in non-human primates.

Westbrook DG, Anderson PG, Pinkerton KE, Ballinger SW - Cardiovasc. Toxicol. (2010)

Bottom Line: Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Mitochondrial DNA (mtDNA) damage in M. mulatta and human buffy coat tissues. MtDNA damage was quantified using QPCR on genomic DNA preparations extracted from M. mulatta and human buffy coats. aBar graph showing the relative level of mtDNA damage (normalized for copy number) in M. mulatta perinatally exposed the ETS compared to unexposed controls. The inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the full-length QPCR product (Long) which is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization, bBar graph showing the relative level of mtDNA damage (normalized for copy number) in human smokers (N = 8) compared to non-smokers (N = 5). The inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the full-length QPCR product (Long) that is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization. Asterisks indicate significant difference (P < 0.05)
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Fig4: Mitochondrial DNA (mtDNA) damage in M. mulatta and human buffy coat tissues. MtDNA damage was quantified using QPCR on genomic DNA preparations extracted from M. mulatta and human buffy coats. aBar graph showing the relative level of mtDNA damage (normalized for copy number) in M. mulatta perinatally exposed the ETS compared to unexposed controls. The inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the full-length QPCR product (Long) which is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization, bBar graph showing the relative level of mtDNA damage (normalized for copy number) in human smokers (N = 8) compared to non-smokers (N = 5). The inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the full-length QPCR product (Long) that is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization. Asterisks indicate significant difference (P < 0.05)

Mentions: To determine whether mtDNA damage was also increased in a surrogate tissue such as blood, DNA was extracted from buffy coat tissues from M. mulatta exposed perinatally to ETS, and also from age-matched human smokers and non-smokers. Figure 4a shows that perinatal cigarette smoke exposure increased mtDNA damage in M mulatta buffy coat DNA (less product in the “long” row on inset reflects more mtDNA damage). Figure 4b reveals that human smokers also had significantly increased mtDNA damage compared to non-smokers, consistent with the notion that tobacco smoke exposure induces mitochondrial damage in humans. Interestingly, perinatal tobacco smoke exposure was also accompanied by a significant decrease in total mtDNA copy number in aorta (Fig. 5), but not blood, in M. mulatta.Fig. 4


Perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in non-human primates.

Westbrook DG, Anderson PG, Pinkerton KE, Ballinger SW - Cardiovasc. Toxicol. (2010)

Mitochondrial DNA (mtDNA) damage in M. mulatta and human buffy coat tissues. MtDNA damage was quantified using QPCR on genomic DNA preparations extracted from M. mulatta and human buffy coats. aBar graph showing the relative level of mtDNA damage (normalized for copy number) in M. mulatta perinatally exposed the ETS compared to unexposed controls. The inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the full-length QPCR product (Long) which is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization, bBar graph showing the relative level of mtDNA damage (normalized for copy number) in human smokers (N = 8) compared to non-smokers (N = 5). The inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the full-length QPCR product (Long) that is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization. Asterisks indicate significant difference (P < 0.05)
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Related In: Results  -  Collection

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Fig4: Mitochondrial DNA (mtDNA) damage in M. mulatta and human buffy coat tissues. MtDNA damage was quantified using QPCR on genomic DNA preparations extracted from M. mulatta and human buffy coats. aBar graph showing the relative level of mtDNA damage (normalized for copy number) in M. mulatta perinatally exposed the ETS compared to unexposed controls. The inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the full-length QPCR product (Long) which is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1–3 are unexposed control, lanes 4–6 are ETS exposed) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization, bBar graph showing the relative level of mtDNA damage (normalized for copy number) in human smokers (N = 8) compared to non-smokers (N = 5). The inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the full-length QPCR product (Long) that is used to quantify relative levels of mtDNA damage (less product indicates increased damage) relative to control, whereas the lower inset (lanes 1, 2 are non-smoker control, lanes 3, 4 are smoker) shows the smaller QPCR product (Short) that is used for mtDNA copy number normalization. Asterisks indicate significant difference (P < 0.05)
Mentions: To determine whether mtDNA damage was also increased in a surrogate tissue such as blood, DNA was extracted from buffy coat tissues from M. mulatta exposed perinatally to ETS, and also from age-matched human smokers and non-smokers. Figure 4a shows that perinatal cigarette smoke exposure increased mtDNA damage in M mulatta buffy coat DNA (less product in the “long” row on inset reflects more mtDNA damage). Figure 4b reveals that human smokers also had significantly increased mtDNA damage compared to non-smokers, consistent with the notion that tobacco smoke exposure induces mitochondrial damage in humans. Interestingly, perinatal tobacco smoke exposure was also accompanied by a significant decrease in total mtDNA copy number in aorta (Fig. 5), but not blood, in M. mulatta.Fig. 4

Bottom Line: Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus