Oxidative stress,mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking |
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| Affiliation: | 1. Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney Medical School, University of Sydney, St Leonards, NSW, Australia;2. School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology, Sydney, Australia;3. Department of Anatomical Pathology, Sydney South West Pathology Service, Liverpool, Australia;4. MQ BioFocus Research Centre, Macquarie University, Sydney, NSW, Australia;1. College of Science, Civil Aviation University of China, Tianjin 300300, China;2. School of Electronics and Information Engineering, Tianjin Polytechnics University, Tianjin 300387, China;1. Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku, Tokyo 162-8601, Japan;2. RIKEN Center for Advanced Photonics, RIKEN, Wako, Saitama 351-0198, Japan;1. Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA;2. Department of Comparative Medicine, The Pennsylvania State University College of Medicine, Hershey, PA;3. Hershey Cancer Institute, The Pennsylvania State University College of Medicine, Hershey, PA;4. Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA;1. School of Medicine, Tongji University, Shanghai, China;2. Department of Endocrine and Metabolic Diseases/ Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;3. Department of VIP Clinic, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China;4. Department of Gastroenterology, Zibo Central Hospital, Zibo, China |
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| 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. |
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| Keywords: | Renal fibrosis Maternal effects Oxidative stress Smoking Mitochondrial function |
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