Ali 2015 Abstract MiP2015

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Mitochondrial function and ROS homeostasis in young mouse heart and brain: the sex factor!

Link:

Khalifa AM, Abdel-Rahman E, Mahmoud AM, Ali MH, Ali SS (2015)

Event: MiP2015

Gender-specific differences in mitochondrial function and free radical homeostasis are consistently reported in the context of aging and associated deficits. However, little is known about the gender-related roles of these parameters in the pathogenesis of neurological and cardiovascular disorders that occur early in life.

Aim: To test the hypothesis that gender disparity in mitochondria function and ROS homeostasis starts early in life and hence can be implicated in sexual dimorphism in some cardiac as well as neurological disorders.

Approach: We investigated heart and brain mitochondrial respiratory function in young (2-4 months) male and female wild-type C57BL6J mice, by high-resolution respirometry. Parallel productions of ROS by respiring mitochondria or active NADPH oxidases (NOXs) were also assessed using high-resolution oxymetry, fluorescence assays, and electron paramagnetic resonance (EPR) spin trapping techniques.

Results: Although mitochondrial respiratory activity in the heart did not significantly vary between genders, female brains exhibited enhanced activity during state 3, state 4, and maximally uncoupled respiration. This was associated with lower rates of hydrogen peroxide production in female cardiac and brain tissues. Furthermore, no gender differences have been detected in Nox2 and Nox4 proteins or activities in brain homogenate or freshly isolated synaptosomes. However, a strong trend of increased EPR-detected NOX-superoxide in male synaptosomes hinted at gender-specific discrepancy in antioxidant enzymes. Indeed, we found that superoxide dismutase (SOD) activity was higher in female brains using two independent approaches.

Conclusion: Taken together, our results indicate that gender differences in mitochondrial bioenergetics and ROS production occur at young age, and that differences in superoxide dismutation capacity may be primarily responsible for gender differences in ROS homeostasis. These findings may eventually assist in the understanding of sexual dimorphism in some disorders that occur early in life.


O2k-Network Lab: EG Cairo Ali SS


Labels: MiParea: Respiration, Gender 


Organism: Mouse  Tissue;cell: Heart, Nervous system  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS, ET 

HRR: Oxygraph-2k, O2k-Fluorometer  Event: C1, Oral  MiP2015 

Affiliations

Center Aging Associated Diseases, Helmy Inst Med Sc, Zewail City Sc Technol, Giza, Egypt. - sameh.ali@zewailcity.edu.eg