HUVECs from newborns with a strong family history of diabetes show diminished ROS synthesis in the presence of high glucose concentrations.
BACKGROUND
A family history of type 2 diabetes mellitus (DM) increases the probability to develop DM and endothelial dysfunction. The probable mechanism involves augmented reactive oxygen species (ROS) synthesis. The aim of this study was to evaluate the synthesis of ROS in human umbilical vein endothelial cells (HUVECs) obtained from healthy newborns with (experimental) and without (control) a strong family history of type 2 DM, exposed to different glucose concentrations.


METHODS
HUVECs were exposed to various glucose concentrations for 24 and 48 h periods, before cell proliferation, mitochondrial activity, and mitochondrial membrane potential were determined. Intracellular ROS synthesis in the presence or absence of the mitochondrial uncoupler CCCP, cytochalasin B, or diphenyleneiodonium (DPI) was also evaluated.


RESULTS
As opposed to control HUVECs, we found that experimental HUVECs exposed to 30 mmol/L glucose showed a 50% decrease in cell proliferation, a 90% reduction in mitochondrial activity, and a statistically significant inhibition of ROS synthesis in the presence of CCCP or cytochalasin B; DPI had no effect.


CONCLUSIONS
Our results suggest that mitochondria and NAD(P)H-oxidase from HUVECs obtained from healthy newborns with a family history of DM have an innate deficient response to high glucose concentrations.
Alvarado-Vásquez
Noé
N
Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, México.
Páez
Araceli
A
Zapata
Estrella
E
Alcázar-Leyva
Susana
S
Zenteno
Edgar
E
Massó
Felipe
F
Montaño
Luis F
LF
D000293:Adolescent; D000328:Adult; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005192:Family Health; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D009861:Onium Compounds; D017382:Reactive Oxygen Species; D003571:Cytochalasin B; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C007517:diphenyleneiodonium; D005947:Glucose