Kim, So Yeon Lee, Myong Jin Kim, Jeong Won Na, Yu-Ran Lee, Ho-Youl Cho, Hyunju Lee, Keun Byeol Lee, You Mie Lee, Cheolju Park, Hyunsung Yang, Eun Gyeong 2024-01-20T13:31:57Z 2024-01-20T13:31:57Z 2021-09-05 2012-12 0918-6158 https://pubs.kist.re.kr/handle/201004/128615 We previously found that clioquinol (CQ) increases functional hypoxia-inducible factor-1 alpha (HIF-1 alpha) with enhanced transcription of its target genes. Here we report that compounds derived from 8-hydroxyquinoline including CQ, broxyquinoline (BQ), iodoquinol (IQ) and chloroacetoxyquinoline (CAQ) promote neovascularization effectively based on chick chorioallantoic membrane assays. The CQ analogues induce stabilization of H IF-1 alpha as well as enhance HIF-1-mediated vascular endothelial growth factor transcription. These analogues also exert inhibitory effects on the activity of prolyl and asparaginyl hydroxylations of H IF-1 alpha in vitro. Despite metal ion-dependent restoration of the inhibited HIF-1 alpha hydroxylase activity, the cellular HIF-1 alpha-inducing effects of the CQ analogues are reversed to varying degrees by Zn2+ and Fe2+. While CQ and BQ are completely reversed by Zn2+, co-administration of Zn2+ and IQ has only a partial reversing effect. On the other hand, CAQ-mediated stabilization of HIF-1 alpha is reversed by Fe2+ but not by Zn2+. These phenomena are found to coincide with elevation of the intracellular Zn2+ and Fe2+ levels by the CQ analogues, suggesting that metal ion effects on H IF-la in cells likely reflect the differential transporting capability of the analogues. English PHARMACEUTICAL SOC JAPAN PROLYL HYDROXYLASE INHIBITORS UBIQUITIN-PROTEASOME PATHWAY ENDOTHELIAL GROWTH-FACTOR THERAPEUTIC TARGET ALZHEIMERS-DISEASE CANCER-THERAPY FACTOR 1-ALPHA FACTOR-I ANGIOGENESIS HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA Effects of Clioquinol Analogues on the Hypoxia-Inducible Factor Pathway and Intracelullar Mobilization of Metal Ions Article 10.1248/bpb.b12-00507 1 BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.35, no.12, pp.2160 - 2169 BIOLOGICAL & PHARMACEUTICAL BULLETIN 35 12 2160 2169 scie scopus 000311772000008 2-s2.0-84871560739 Pharmacology & Pharmacy Pharmacology & Pharmacy Article PROLYL HYDROXYLASE INHIBITORS UBIQUITIN-PROTEASOME PATHWAY ENDOTHELIAL GROWTH-FACTOR THERAPEUTIC TARGET ALZHEIMERS-DISEASE CANCER-THERAPY FACTOR 1-ALPHA FACTOR-I ANGIOGENESIS HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA 8-hydroxyquinoline derivative hypoxia-inducible factor-1 alpha zinc ion prolyl hydroxylase domain 2 factor-inhibiting hypoxia-inducible factor-1 angiogenesis