formazans and Mitochondrial-Diseases

Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.

Topics: Analysis of Variance; Animals; Anthocyanins; Apoptosis; Blotting, Western; Cell Proliferation; Chromatography, High Pressure Liquid; Endothelial Cells; Female; Flow Cytometry; Formazans; Glucosides; Human Umbilical Vein Endothelial Cells; Humans; Lipoproteins, LDL; Mice; Mice, Inbred BALB C; Mitochondrial Diseases; Molecular Structure; Reactive Oxygen Species; Sodium-Glucose Transporter 1; Spectrometry, Fluorescence; Tetrazolium Salts

To examine the protective effect of green tea polyphenols against ultraviolet B (UVB)-induced damage to retinal pigment epithelial (RPE) cells.. Green tea polyphenols (GTP) was used to treat RPE cells before or after exposure to UVB. Viability of RPE cells was tested by 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Survivin gene expression was examined by real-time PCR analysis. Ultrastructure of RPE cells was examined by transmission electron microscopy.. GTP effectively suppressed the decrease in viability of the UVB stressed RPE cells and the UVB suppression of survivin gene expression level. GTP alleviated mitochondria dysfunction and DNA fragmentation induced by UVB.. GTP protected RPE cells from UVB damage through its increase in the survivin gene expression and its attenuation of mitochondria dysfunction and DNA fragmentation. GTP is a potential candidate for further development as a chemoprotective factor for the primary prevention of age-related eye diseases such as age-related macular degeneration.

Topics: Camellia sinensis; Cell Survival; Cells, Cultured; DNA Fragmentation; Flavonoids; Formazans; Gene Expression; Humans; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins; Mitochondrial Diseases; Phenols; Polyphenols; Radiation-Protective Agents; Retinal Pigment Epithelium; Reverse Transcriptase Polymerase Chain Reaction; Survivin; Tea; Tetrazolium Salts; Ultraviolet Rays