Opioid receptor stimulation does not affect cellular hypoxia-induced gene responses mediated by hypoxia-inducible factor 1 in cultured cell lines.
Hypoxia induces a series of adaptive physiological responses including gene inductions. Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that regulates hypoxia-induced gene expression to maintain homeostasis in the living body. Opioids are potent analgesic agents that are widely used in clinical practice. Therefore, we investigated the effect of opioids on HIF-1 activity. SH-SY5Y human neuronal cells, which express opioid receptors intrinsically, were cultured under 1% or 20% O2 conditions with or without treatment by DAGO, DPDPE, or U-50488, which are the selective agonists of mu-, delta-, and kappa-opioid receptors, respectively. Expression of subunits of HIF-1, HIF-1alpha, and HIF-1beta were examined by Western blot using specific antibodies. Expression of the HIF-1-dependent gene were investigated by reporter assay. None of the selective agonists of opioid receptors tested affected HIF-1 activation by hypoxia. Therefore, it is suggested that opioid receptor-mediated signals do not affect HIF-1-dependent cellular hypoxia-induced gene responses.
Takabuchi
Satoshi
S
Department of Anesthesia, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Hirota
Kiichi
K
Oda
Seiko
S
Nishi
Kenichiro
K
Oda
Tomoyuki
T
Shingu
Koh
K
Adachi
Takehiko
T
Fukuda
Kazuhiko
K
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D015687:Cell Hypoxia / Q000235:genetics*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects; D011957:Receptors, Opioid / Q000819:agonists*; D013268:Stimulation, Chemical; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D043562:Receptors, G-Protein-Coupled; D011957:Receptors, Opioid; D014157:Transcription Factors; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-