Induction of endothelial cell cytoplasmic lipid bodies during hypoxia.
Lipid bodies (LBs), lipid-rich cytoplasmic inclusions found in many cell types, seem to act as nonmembrane sites of eicosanoid formation. Because alterations in eicosanoid products have been demonstrated in endothelial cells (ECs) during hypoxia, we investigated induction of LBs in systemic and pulmonary ECs exposed to acute and/or chronic hypoxia. LBs in ECs were O(2)-concentration dependent, increasing approximately fivefold during acute exposure to 0% O(2) in both cell types. During chronic exposure to 3% O(2), LBs were induced only in systemic ECs. LBs were not induced by other cellular stresses (heat shock or glucose deprivation). Subsequent studies suggested that protein kinase C-dependent and tyrosine kinase-dependent pathways are important in LB induction during hypoxia. PGH synthase was demonstrated in LBs in every case in which they were induced. These are the initial studies to demonstrate induction of LBs in ECs and to demonstrate LB induction during exposure to hypoxia in any cell type. These results imply that in ECs, LBs are structurally distinct inducible sites for synthesis of eicosanoid mediators.
Scarfo
L M
LM
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Weller
P F
PF
Farber
H W
HW
D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D004396:Coloring Agents; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D015777:Eicosanoids / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005947:Glucose / Q000172:deficiency; D018869:Heat-Shock Response; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D050356:Lipid Metabolism; D010100:Oxygen / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D004396:Coloring Agents; D015777:Eicosanoids; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; D010100:Oxygen