The loading scores of cysteine-glutathione disulfide (CysGTdS), thiamine, nicotinamide, gluconic acid, Cys, gluconic acid, and hypoxanthine
were highly positive for PC1 (Table 2).
In addition to the lipid metabolism, we observed that xanthine and hypoxanthine
significantly changed across the three time points.
Blockage of this pathway leads to accumulation of the uric acid precursors xanthine and hypoxanthine
, of which hypoxanthine
is more soluble and more easily excreted than uric acid.
The conversion of hypoxanthine
to uric acid is regulated by XO.16 However XO is produced by liver and small intestine but evidence showed that XO can also be produced locally by myocardium in many cardiac disease related to the oxidative stress such as left ventricular remodeling.17 ROS can also be generated by XO which cause cytotoxicity in physiological and pathological conditions.18 However, ROS can also damage the myocardial tissue due to the increased rate of apoptosis and other cardiac complications.19-21
Differences were observed for storage times in all studied variables; however, differences between the treatments were observed for IMP (inosine monophosphate), ATP (adenosine triphosphate), ADP (adenosine diphosphate), AMP (adenosine monophosphate) and Hx (hypoxanthine
) (Figure 4).
Human endothelial cells contain cytoplasmic and membrane-bound XO, capable of producing [O.sup.-.sub.2] and [H.sub.2][O.sub.2], depending on whether the substrate is xanthine or hypoxanthine
. In circulation, XO can also produce ROS, thereby imposing injury to vascular endothelial and other cells in close proximity, for example adhered neutrophils.
Gl 1950) and hypoxanthine
(Sigma Aldrich, catalog no.
HPLC methods for simultaneous quantification of creatinine, uric acid, and hypoxanthine
have been reported.
NG108-15 cells (obtained from China Center for Type Culture Collection (CCTCC), Wuhan, China) were cultured in Dulbecco's modified essential media (DMEM) (GIBCO) supplemented with 10% (v/v) FBS (GIBCO) and 1 x HAT (100 [micro]M hypoxanthine
, 0.4 [micro]M aminopterin, and 16 [micro]M thymidine) (H0262, Sigma).
Ischemia-induced tissue hypoxia has been proven to result in the conversion of xanthine dehydrogenase to XO and breakdown of ATP to hypoxanthine
in turn acts as a substrate for XO to produce a mass of superoxide, hydrogen peroxide, hydroxyl radicals, and uric acid during restoration of oxygen supply .
Standard curves were constructed for adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 57-monophosphate (AMP), inosine 5'-monophosphate (IMP), inosine (Ino), and hypoxanthine
(Hx) (Sigma-Aldrich, USA).
Berg et al., "Isolation and characterization of a full-length expressible cDNA for human hypoxanthine
phosphoribosyl transferase," Proceedings of the National Academy of Sciences of the United States of America, vol.