Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring.
Nicole G BarraMaria LisyanskyTaylor A VanduzerSandeep RahaAlison C HollowayDaniel B HardyPublished in: Journal of applied toxicology : JAT (2017)
Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also occur in the heart. At 3 months of age, nicotine-exposed offspring had 45% decreased PDI levels in the absence of endoplasmic reticulum stress. Given the association of PDI and superoxide dismutase enzymes, we further observed that antioxidant superoxide dismutase-2 levels were reduced by 32% in these offspring concomitant with a 26-49% decrease in mitochondrial complex proteins (I, II, IV and V) and tissue inhibitor of metalloproteinase-4, a critical matrix metalloprotease for cardiac contractility and health. Collectively, this study suggests that perinatal nicotine exposure decreases PDI, which can promote oxidative damage and mitochondrial damage, associated with a premature decline in cardiac function.
Keyphrases
- smoking cessation
- endoplasmic reticulum stress
- oxidative stress
- induced apoptosis
- blood pressure
- replacement therapy
- high fat diet
- left ventricular
- heart failure
- healthcare
- preterm birth
- traumatic brain injury
- hydrogen peroxide
- gestational age
- nitric oxide
- risk factors
- metabolic syndrome
- risk assessment
- body mass index
- birth weight
- signaling pathway
- pregnancy outcomes
- weight gain