Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking

Stefanie Stangenberg, Long T. Nguyen, Hui Chen, Ibrahim Al-Odat, Murray C. Killingsworth, Martin E. Gosnell, Ayad G. Anwer, Ewa M. Goldys, Carol A. Pollock, Sonia Saad*

*Corresponding author for this work

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume64
DOIs
Publication statusPublished - 1 Jul 2015

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