Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring. Issue 12 (6th July 2017)

• Record Type: Journal Article
• Authors: Barra, Nicole G.; Lisyansky, Maria; Vanduzer, Taylor A.; Raha, Sandeep; Holloway, Alison C.; Hardy, Daniel B.
• Is Part Of: Journal of applied toxicology. Volume 37:Issue 12(2017)
• Page Start: 1517
• Page End: 1526
• Publication Date: 2017-07-06
• Subjects: heart -- mitochondria -- perinatal nicotine exposure -- protein disulfide isomerase; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3503
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: 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. Abstract : Although nicotine replacement therapies are considered safer than smoking, recent rodent studies suggest that perinatal nicotine exposure results in cardiac dysfunction; however, the underlying mechanisms are not completely understood. Our study demonstrates that perinatal nicotine exposed male rats at 3 months have a significant decrease in cardiac protein disulfide isomerase, superoxide dismutase 2, tissue inhibitor of metalloproteinase 4 and mitochondrial complex protein expression. This suggests that nicotine may indirectly disrupt cardiac function by decreasing protein disulfide isomerase expression, leading to oxidative damage and mitochondrial damage.