%0 Journal Article
%A Selen, Ebru Selin
%A Bolandnazar, Zeinab
%A Tonelli, Marco
%A Bütz, Daniel
E.
%A Haviland, Julia A.
%A Porter, Warren P.
%A Assadi-Porter, Fariba M.
%D 2015
%T NMR Metabolomics
Show Evidence for Mitochondrial Oxidative
Stress in a Mouse Model of Polycystic Ovary Syndrome
%U https://acs.figshare.com/articles/journal_contribution/NMR_Metabolomics_Show_Evidence_for_Mitochondrial_Oxidative_Stress_in_a_Mouse_Model_of_Polycystic_Ovary_Syndrome/2143282
%R 10.1021/acs.jproteome.5b00307.s001
%2 https://acs.figshare.com/ndownloader/files/3777133
%K NAD
%K Polycystic Ovary SyndromePolycystic ovary syndrome
%K plasma
%K NMR Metabolomics Show Evidence
%K acid
%K PP
%K disorder
%K 16 weeks
%K NADH
%K TCA cycle metabolism
%K PCOS
%K mitochondrial oxidative stress
%K Mitochondrial Oxidative Stress
%K biomarker
%X Polycystic
ovary syndrome (PCOS) is associated with metabolic and
endocrine disorders in women of reproductive age. The etiology of
PCOS is still unknown. Mice prenatally treated with glucocorticoids
exhibit metabolic disturbances that are similar to those seen in women
with PCOS. We used an untargeted nuclear magnetic resonance (NMR)-based
metabolomics approach to understand the metabolic changes occurring
in the plasma and kidney over time in female glucocorticoid-treated
(GC-treated) mice. There are significant changes in plasma amino acid
levels (valine, tyrosine, and proline) and their intermediates (2-hydroxybutyrate,
4-aminobutyrate, and taurine), whereas in kidneys, the TCA cycle metabolism
(citrate, fumarate, and succinate) and the pentose phosphate (PP)
pathway products (inosine and uracil) are significantly altered (p < 0.05) from 8 to 16 weeks of age. Levels of NADH,
NAD+, NAD+/NADH, and NADH redox in kidneys indicate
increased mitochondrial oxidative stress from 8 to 16 weeks in GC-treated
mice. These results indicate that altered metabolic substrates in
the plasma and kidneys of treated mice are associated with altered
amino acid metabolism, increased cytoplasmic PP, and increased mitochondrial
activity, leading to a more oxidized state. This study identifies
biomarkers associated with metabolic dysfunction in kidney mitochondria
of a prenatal gluococorticoid-treated mouse model of PCOS that may
be used as early predictive biomarkers of oxidative stress in the
PCOS metabolic disorder in women.
%I ACS Publications