title: Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking.
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.
authors: Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical School, University of Sydney, St Leonards, NSW, Australia.
authors: Stefanie
authors: S
authors: Stangenberg
authors: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology, Sydney, Australia.
authors: Long T
authors: LT
authors: Nguyen
authors: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology, Sydney, Australia.
authors: Hui
authors: H
authors: Chen
authors: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology, Sydney, Australia.
authors: Ibrahim
authors: I
authors: Al-Odat
authors: Department of Anatomical Pathology, Sydney South West Pathology Service, Liverpool, Australia.
authors: Murray C
authors: MC
authors: Killingsworth
authors: MQ BioFocus Research Centre, Macquarie University, Sydney, NSW, Australia.
authors: Martin E
authors: ME
authors: Gosnell
authors: MQ BioFocus Research Centre, Macquarie University, Sydney, NSW, Australia.
authors: Ayad G
authors: AG
authors: Anwer
authors: MQ BioFocus Research Centre, Macquarie University, Sydney, NSW, Australia.
authors: Ewa M
authors: EM
authors: Goldys
authors: Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical School, University of Sydney, St Leonards, NSW, Australia.
authors: Carol A
authors: CA
authors: Pollock
authors: Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical School, University of Sydney, St Leonards, NSW, Australia. Electronic address: sonia.saad@sydney.edu.au.
authors: Sonia
authors: S
authors: Saad
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D013482:Superoxide Dismutase
keywords: Maternal effects; Mitochondrial function; Oxidative stress; Renal fibrosis; Smoking