Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Marine Product Preparation
2.2. Luciferase Assay for Fish Screening
2.3. Real-Time PCR
2.4. Western Blotting
2.5. Animals
2.6. Oxygen-Induced Retinopathy Model and Administration of Fish Gradients
2.7. Statistical Analysis
3. Results
3.1. In Vitro Screening for Hypoxia-Inducible Factor (HIF) Inhibitors from Marine Products
3.2. Screened Fish Ingredients Inhibit HIF and HIF Target Genes In Vitro
3.3. Fish Ingredients Suppressed Neovascularization in a Murine Oxygen-Induced Retinopathy (OIR) Model
4. Discussion
5. Conclusions
6. Patents
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Species of Fish | Japanese Name | Sampling Parts | Rate of Change (%) |
---|---|---|---|
Scomber australasicus | Gomasaba | white muscle, dorsal | −75.0 |
Fermented dried bonito | Honkare-bushi | - | −70.9 |
Dried bonito | Ara-bushi | - | −70.9 |
Katsuwonus pelamis | Katsuo | white muscle, dorsal | −68.0 |
Scomber japonicus | Masaba | white muscle, dorsal | −68.0 |
Thunnus obesus | Mebachi | white muscle, dorsal | −65.0 |
Etrumeus teres | Urumeiwashi | skinless fillet | −56.5 |
Cypselurus agoo | Tobiuo | white muscle, dorsal | −55.8 |
Dried mackerel | Saba-bushi | - | −50.5 |
Spratelloides gracilis | Kibinago | headless | −49.5 |
Thunnus obesus | Mebachi | head muscle | −49.5 |
Trachurus japonicus | Maaji | skinless fillet | −47.6 |
Topotecan † | - | - | −40.0 |
Thunnus obesus | Mebachi | Pectoral fin muscle | −39.8 |
Scomberomorus niphonius | Sawara | white muscle, dorsal | −38.8 |
Doxorubicin † | - | - | −37.5 |
Selar crumenophthalmus | Meaji | skinless fillet | −35.5 |
Sardinops melanostictus | Maiwasi | whole | −33.3 |
Decapterus macarellus | Kusayamoro | skinless fillet | −31.0 |
Seriola dumerili | Kanpachi | white muscle, dorsal | −26.5 |
Coryphaena hippurus | Siira | white muscle, dorsal | −25.0 |
Pagrus major | Madai | white muscle, dorsal | −24.3 |
Dried sardine | Iwashi-bushi | - | −24.3 |
Rhabdosargus sarba | Hedai | white muscle, dorsal | −23.7 |
Panulirus japonicus | Ise-ebi | muscle, abdomen | −14.5 |
Seriola quinqueradiata | Buri | white muscle, dorsal | −11.5 |
Haliotis diversicolor aquatilis | Tokobushi | muscle, foot | −10.0 |
Scomberoides lysan | Ikekatsuo | skinless fillet | −4.9 |
Marsupenaeus japonicus | Kuruma-ebi | muscle, abdomen | −0.0 |
CoCl2 | - | - | 0 |
Species of Fish | Japanese Name | Sampling Parts | Rate of Change (%) |
---|---|---|---|
CoCl2 | - | - | 0 |
Oncorhynchus mykiss | Nijimasu | white muscle, dorsal | 1.9 |
Lateolabrax latus | Hirasuzuki | white muscle, skinless fillet | 4.4 |
Crassostrea gigas | Magaki | edible part | 8.0 |
Haliotis gigantea | Megai-awabi | muscle, foot | 9.5 |
Gerres equulus | Kurosagi | white muscle, skinless fillet | 12.5 |
Caranx sexfasciatus | Gingameaji | skinless fillet | 16.9 |
Plecoglossus altivelis altivelis | Ayu | skinless fillet | 17.4 |
Dasyatis akajei | Akaei | white muscle, dorsal | 24.5 |
Caranx ignobilis | Rounin-aji | skinless fillet | 29.9 |
Charonia lampas sauliae | Boushu-bora | muscle, foot | 30.5 |
Oplegnathus punctatus | Ishigakidai | white muscle, dorsal | 36.5 |
Plectorhinchus cinctus | Koshodai | white muscle, skinless fillet | 39.5 |
Guinusia dentipes | Shojin-kani | muscle, cheliped and ambulatory leg | 39.5 |
Girella punctata | Mejina | white muscle, dorsal | 44.0 |
Stephanolepis cirrhifer | Kawahagi | white muscle, skinless fillet | 47.0 |
Lateolabrax japonicus | Suzuki | white muscle, skinless fillet | 53.0 |
Scombrops boops | Mutu | headless | 75.0 |
Paralichthys olivaceus | Hirame | white muscle, skinless fillet | 77.0 |
Turbo sazae | Sazae | muscle, foot | 80.0 |
Meretrix lusoria | Hamaguri | edible part | 83.0 |
Sphyraena japonica | Yamatokamasu | white muscle, dorsal | 87.5 |
Oncorhynchus masou ishikawae | Amago | skinless fillet | 88.5 |
Ruditapes philippinarum | Asari | edible part | 96.5 |
Anguilla japonica | Nihon-unagi | skinless fillet | 98.1 |
Sphyraena pinguis | Akakamasu | white muscle, dorsal | 104.2 |
Siganus fuscescens | Aigo | white muscle, dorsal | 104.2 |
Heteropriacanthus cruentatus | Gomahirekintoki | white muscle, skinless fillet | 105.5 |
Trichiurus japonicus | Tachiuo | white muscle, skinless fillet | 108.5 |
Prionurus scalprum | Nizadai | white muscle, dorsal | 117.5 |
Diaphus suborbitalis | Senhadaka | headless | 127.7 |
Stichopus japonica | Manamako | muscle | 129.5 |
Beryx splendens | Kinmedai | white muscle, dorsal | 133.0 |
Chelidonichthys spinosus | Houbou | white muscle, skinless fillet | 134.0 |
Siganus fuscescens | Aigo | ovary | 142.5 |
Parapristipoma trilineatum | Isaki | white muscle, skinless fillet | 147.5 |
Goniistius zonatus | Takanohadai | white muscle, dorsal | 147.5 |
Calotomus japonicus | Budai | white muscle, dorsal | 149.0 |
Engraulis japonica | Katakuchi-iwashi | whole (larva) | 180.0 |
Konosirus punctatus | Konoshiro | white muscle, skinless fillet | 182.0 |
Lucensosergia lucens | Sakura-ebi | whole | 215.8 |
Sphyraena pinguis | Akakamasu | testis | 230.8 |
Species of Fish | Japanese Name | Sampling Parts | Rate of Change (%) | p Value |
---|---|---|---|---|
DMOG | - | - | 0 | - |
Fermented dried bonito | Honkare-bushi | - | 1.0 | 0.999 |
Seriola quinqueradiata | Buri | white muscle, dorsal | 3.8 | 0.871 |
Coryphaena hippurus | Siira | white muscle, dorsal | 6.3 | 0.826 |
Thunnus obesus | Mebachi | white muscle, dorsal | 7.7 | 0.919 |
Cypselurus agoo | Tobiuo | white muscle, dorsal | 8.2 | 0.882 |
Dried sardine | Iwashi-bushi | - | 10.9 | 0.039 |
Scomber australasicus | Gomasaba | white muscle, dorsal | 11.1 | 0.529 |
Sardinops melanostictus | Maiwasi | whole | 11.5 | 0.464 |
Katsuwonus pelamis | Katsuo | white muscle, dorsal | 13.9 | 0.206 |
Pagrus major | Madai | white muscle, dorsal | 15.9 | 0.011 * |
Scomber japonicus | Masaba | white muscle, dorsal | 21.6 | 0.004 ** |
Dried mackel | Saba-bushi | - | 26.9 | 0.0002 *** |
Scomberomorus niphonius | Sawara | white muscle, dorsal | 28.4 | 0.0001 *** |
Etrumeus teres | Urumeiwashi | skinless fillet | 69.0 | 0.00004 † |
Thunnus obesus | Mebachi | head muscle | 70.4 | 0.00002 † |
Thunnus obesus | Mebachi | pectoral fin muscle | 79.5 | 0.000005 ‡ |
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Species of Fish | Japanese Name | Sampling Parts | Rate of Change (%) | p value |
---|---|---|---|---|
Topotecan † | - | - | −54.4 | 0.0000000 ‡ |
Doxorubicin † | - | - | −54.4 | 0.0000000 ‡ |
Selar crumenophthalmus | Meaji | skinless fillet | −47.2 | 0.0000001 ‡ |
Seriola dumerili | Kanpachi | white muscle, dorsal | −29.0 | 0.00003 † |
Spratelloides gracilis | Kibinago | headless | −27.9 | 0.0003 *** |
Decapterus macarellus | Kusayamoro | skinless fillet | −24.4 | 0.0001 *** |
Panulirus japonicus | Ise-ebi | muscle, abdomen | −17.2 | 0.069 |
Sulculus diversicolo supertexta | Tokobushi | Muscle, foot | −12.2 | 0.283 |
Trachurus japonicus | Maaji | skinless fillet | −8.8 | 0.127 |
Dried bonito | Ara-bushi | - | −3.8 | 0.999 |
Scomberoides lysan | Ikekatsuo | skinless fillet | −2.9 | 0.999 |
Rhabdosargus sarba | Hedai | white muscle, dorsal | −1.4 | 0.999 |
DMOG | - | - | 0 | - |
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Shoda, C.; Miwa, Y.; Nimura, K.; Okamoto, K.; Yamagami, S.; Tsubota, K.; Kurihara, T. Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy. Nutrients 2020, 12, 1055. https://doi.org/10.3390/nu12041055
Shoda C, Miwa Y, Nimura K, Okamoto K, Yamagami S, Tsubota K, Kurihara T. Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy. Nutrients. 2020; 12(4):1055. https://doi.org/10.3390/nu12041055
Chicago/Turabian StyleShoda, Chiho, Yukihiro Miwa, Kazumi Nimura, Kazutoshi Okamoto, Satoru Yamagami, Kazuo Tsubota, and Toshihide Kurihara. 2020. "Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy" Nutrients 12, no. 4: 1055. https://doi.org/10.3390/nu12041055