Hypoxia inhibits the SDF-1-dependent migration of human leukemic cell line HL-60 via blocking of Akt activation.
Hypoxia is known to regulate the expression of genes involved in the migration of various cell types. Although many studies have shown that hypoxia increases cell migration, it still remains unclear whether hypoxia could modulate the stromal cell derived factor-1 (SDF-1)-dependent migration of leukemic cell. Herein, we demonstrated that the SDF-1-dependent migration of HL-60, was reduced under hypoxia with no comparable decrease of CXC-type chemokine receptor CXCR4, a cognate receptor for SDF-1. Furthermore, we showed that migration toward SDF-1 was reduced by inactivation of either serine/threonine kinase Akt or extracellular signal regulated kinase Erk, which was confirmed by selective pathway inhibitor LY294002 and PD98059. In our results, phosphorylation of Erk was increased under hypoxia, but phosphorylation of Akt was attenuated on the contrary. These results led us to conclusion that hypoxia could inhibit the SDF-1-dependent migration of HL-60 via blocking of Akt activation.
Seo
Young-Jin
YJ
Laboratory of Immunology, School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
Koh
Sang Hyeok
SH
Kang
Hyoung Jin
HJ
Shin
Hee Young
HY
Jeong
Gajin
G
Ahn
Hyo Seop
HS
D015687:Cell Hypoxia; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000096:biosynthesis
D054377:Chemokine CXCL12; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009025:Morpholines; D019718:Receptors, CXCR4; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one