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

Int J Biochem Cell Biol. 2015 Jul:64:81-90. doi: 10.1016/j.biocel.2015.03.017. Epub 2015 Apr 4.

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.

Keywords: Maternal effects; Mitochondrial function; Oxidative stress; Renal fibrosis; Smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism*
  • Lysosomes / metabolism
  • Mice, Inbred BALB C
  • Mitochondria / enzymology
  • Mitochondria / pathology
  • Oxidative Phosphorylation
  • Oxidative Stress*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / metabolism
  • Smoking / adverse effects*
  • Smoking / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • Superoxide Dismutase