Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro.
Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro study we compared the effects of hypoxia and Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) under different hypoxic conditions (3% and nearly 0% O2) and Co2+ -concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1alpha protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). however, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (> or =0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+ -exposure took place, further yet unknown Co2+ -induced event(s) must have occurred.
Peters
Kirsten
K
Institute of Pathology, Johannes Gutenberg-University, Langenbeckstr. 1, 55101 Mainz, Germany. peters@pathologie.klinik.uni-mainz.de
Schmidt
Harald
H
Unger
Ronald E
RE
Kamp
Günter
G
Pröls
Felicitas
F
Berger
Bernhard J
BJ
Kirkpatrick
C James
CJ
D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D003035:Cobalt / Q000378:metabolism / Q000494:pharmacology*; D004396:Coloring Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005840:Gentian Violet / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007477:Ions; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012984:Software; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D004396:Coloring Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007477:Ions; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D005840:Gentian Violet; D010100:Oxygen