Different response of cerebral and non-cerebral endothelial cells to cytotoxic hypoxia.
The present study investigated the effect of cytotoxic hypoxia on cerebral and non-cerebral endothelial cells. Hypoxia was induced by inhibiting the cellular respiratory chain with 1 mM sodium cyanide. Cerebral endothelial cells were damaged after 2 h of hypoxia as assessed by a decrease in cell viability by 25% and by a 2.7-fold higher lactate dehydrogenase release compared to controls. Additional glucose deprivation did not significantly exacerbate hypoxic injury. In addition, we found after 2 h of hypoxia an increase in the release of lactate of 1.02 and 0.42 mg/mg protein compared to 0.27 and 0.07 mg/mg protein in controls in the presence and absence of glucose, respectively. While the activity of ALP of cerebral endothelial cells was maintained at the control level, we found a significant decrease in the gamma-GT activity from 3.8 +/- 1.3 to 1.09 +/- 0.3 U/mg protein after 3 h of hypoxia in the presence as well as in the absence of glucose. The paracellular permeability of the cell monolayer decreased after 1 h and returned to control level after 3 h of hypoxia in the presence of glucose. Non-cerebral endothelial cells remained 98% viable with no change in the release of lactate dehydrogenase and lactate after 2 h of hypoxia in the presence and absence of glucose. The activities of ALP and gamma-GT in non-cerebral endothelial cells were 10 and 3 times lower and remained unchanged during hypoxia. We conclude from our experiments that sodium cyanide is useful to study hypoxic injury and that cerebral endothelial cells are more sensitive than non-cerebral endothelial cells to cytotoxic hypoxia.
Ahlemeyer
B
B
Institut für Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, Dresden, Germany.
Brust
P
P
Johannsen
B
B
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D012966:Sodium Cyanide / Q000633:toxicity*; D013552:Swine; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D012966:Sodium Cyanide