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Ghada Al-Kafaji

Ghada Al-Kafaji

Arabian Gulf Univeristy, Bahrain

Title: Defects of mitochondrial genome in diabetic nephropathy: Role and clinical relevance

Biography

Biography: Ghada Al-Kafaji

Abstract

Mitochondria play important roles in cellular energy metabolism and reactive oxygen species (ROS) generation. Hyperglycemia-induced overproduction of mitochondrial ROS contributes to mitochondrial dysfunction and the development diabetic complication, including diabetic nephropathy (DN). We investigated changes in the mitochondrial DNA copy number (mtDNA-CN), gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes and mitochondrial biogenesis in DN.

ROS production, mitochondrial function, mtDNA-CN, gene expression of mtDNA-encoded ETC subunits and mitochondrial biogenesis regulatory factors were analysed in human mesangial cells cultured for 1, 4, and 7 days in normal and high glucose in the presence and absence of manganese superoxide dismutase mimic (MnTBAP) or catalase. Additionally, mtDNA-CN was analysed in peripheral blood of type 2 diabetes (T2D) patients with normoalbuminuria, DN patients with microalbuminuria or macroalbuminuria and healthy control subjects.

In the renal cells, high glucose induced a significant increase in ROS production, which was accompanied by a progressive decrease in ATP. mtDNA-CN, expression of mtDNA-encoded genes and mitochondrial biogenesis were increased at 1 day in high glucose but were decreased at 4 and 7 days. Treatment of cells with MnTBAP or catalase during high-glucose incubation attenuated ROS production and all these changes. In the subject groups, peripheral blood mtDNA-CN was significantly lower in DN patients compared with T2D patients and controls, declined with the severity of DN, and showed a significant diagnostic ability to differentiate DN patients from T2D patients and healthy controls. Lower mtDNA-CN was independently associated with the progression of DN, negatively correlated with albuminuria and conventional risk factors of DN, and positively correlated with eGFR.

Our data show that defects of mitochondrial genome paly important role in DN. Protection of mitochondria from high glucose-induced ROS may provide a potential approach to retard the development of DN. Our data also propose the mtDNA-CN as a novel blood biomarker for the early diagnosis of DN and the significance of decreased mtDNA-CN as another risk factor in the development of DN.

 

Recent publications

  1. Al-Kafaji G, AlJadaan A, Kamal A, Bakhiet M (2018). Peripheral blood mitochondrial DNA copy number is a potential new biomarker for diabetic nephropathy in type 2 diabetes patients. International Journal of Molecular Medicine. In press, Manuscript number: 204218.
  2. Al-Kafaji G, Sabry MA, Skrypnyk C (2016). Time-course effect of high glucose-induced reactive oxygen species on mitochondrial biogenesis and function in human renal mesangial cells. Cell Biology International  40(1):36-48.
  3. Al-Kafaji G, Sabry MA, Bakhiet M (2016). Increased expression of mitochondrial DNA-encoded genes in human renal mesangial cells in response to high glucose-induced reactive oxygen species. Molecular Medicine Reports 13(2):1774-80.
  4. Al-Kafaji G, Golbahar J (2013). High glucose-induced oxidative stress increases the copy number of mitochondrial DNA in human mesangial cells. Biomedical Research International 2013:754946.