HIF1A

=== HIF-1α in fish physiology ===

=== HIF-1α in fish physiology ===

In an attempt to maintain homeostasis and compensate with hypoxic conditions, fish will upregulate HIF-1α and other stress related genes. HIF-1α has been used in numerous studies to quantify the biochemical changes that occur within fish tissue before, during, and after hypoxia exposure. One study analyzing the effects of progressive hypoxia and reoxygenation in Korean Black rockfish (''Sebastes schlegelii''), showed that HIF-1a mRNA in gill and liver were significantly upregulated at loss of equilibrium (LOE) and 50% lethal time (LT50).{{Cite journal |last=Jia |first=Yudong |last2=Gao |first2=Yuntao |last3=Wan |first3=Jinming |last4=Gao |first4=Yunhong |last5=Li |first5=Juan |last6=Guan |first6=Changtao |date=2021-08-01 |title=Altered physiological response and gill histology in black rockfish, Sebastes schlegelii, during progressive hypoxia and reoxygenation |url=https://doi.org/10.1007/s10695-021-00970-5 |journal=Fish Physiology and Biochemistry |language=en |volume=47 |issue=4 |pages=1133–1147 |doi=10.1007/s10695-021-00970-5 |issn=1573-5168}} One study showed that flatfish turbot (''Scophthalmus maximus)'' increased gene expression in the hif pathway (hif-1α,hif-2α, hif-3α) under acute hypoxia as they attempted to compensate for the lack of DO in the environment. Flatfish are generally known to be more hypoxia tolerant and efficient at regulating low oxygenated environments than other fish. {{Cite journal |last1=Ma|first1=Qiang|last2=Xu|first2=Houguo|last3=Wei|first3=Yuliang|last4=Liang|first4=Mengqing|date=2024-02-01|title=Effects of acute hypoxia on nutrient metabolism and physiological function in turbot, Scophthalmus maximus|url=https://doi.org/10.1007/s10695-022-01154-5|journal=Fish Physiology and Biochemistry|language=en|volume=50|issue=1|pages=367–383|doi=10.1007/s10695-022-01154-5|pmid=36609890 |bibcode=2024FPBio..50..367M |issn=1573-5168}}{{Cite journal |last=Tunnicliffe |first=Verena |last2=Gasbarro |first2=Ryan |last3=Juanes |first3=Francis |last4=Qualley |first4=Jessica |last5=Soderberg |first5=Nicole |last6=Chu |first6=Jackson W. F. |date=2020-02 |title=An hypoxia‐tolerant flatfish: consequences of sustained stress on the slender sole Lyopsetta exilis (Pleuronectidae) in the context of a changing ocean |url=https://onlinelibrary.wiley.com/doi/10.1111/jfb.14212 |journal=Journal of Fish Biology |language=en |volume=96 |issue=2 |pages=394–407 |doi=10.1111/jfb.14212 |issn=0022-1112 |pmc=7028253 |pmid=31755100}} At the proteomic level, fat greenling (''Hexagrammos otakii)'', showed increased levels of HIF-1α protein when oxygen levels were 2.2 ± 0.2 DO mg/L for 6 hours, 12 hours, 24 hours, and at 48 hours, compared with the control group at 7.8 ± 0.2 DO mg/L using qRT-PCR and ELISA assays. Furthermore, HIF-1a was also correlated with hemoglobin (HB), ERO-1α, and lactic acid (LA) showing how it is involved with other metabolites {{Cite journal |last1=Zhan|first1=Yu|last2=Qi|first2=Xin|last3=Wu|first3=Yiting|last4=Gao|first4=Dongxu|last5=Zhao|first5=Ling|last6=Cao|first6=Shengnan|last7=Xue|first7=Zhuang|last8=Wang|first8=Wei|date=2024-12-01|title=Hypoxia-inducible factor-1α as a biomarker for individuals under hypoxia duration and pattern in fat greenling Hexagrammos otakii|url=https://www.sciencedirect.com/science/article/pii/S2352513424005477|journal=Aquaculture Reports|volume=39|article-number=102459|doi=10.1016/j.aqrep.2024.102459|bibcode=2024AqRep..3902459Z |issn=2352-5134}} However, this upregulation in HIF introduces energetic trade-offs that may inhibit other cellular functions such as mitochondrial oxygen consumption and disruption of the citric acid cycle. {{Cite journal |last1=Papandreou|first1=Ioanna|last2=Cairns|first2=Rob A.|last3=Fontana|first3=Lucrezia|last4=Lim|first4=Ai Lin|last5=Denko|first5=Nicholas C.|date=March 2006|title=HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption|url=https://linkinghub.elsevier.com/retrieve/pii/S155041310600060X|journal=Cell Metabolism|volume=3|issue=3|pages=187–197|doi=10.1016/j.cmet.2006.01.012|pmid=16517406 |issn=1550-4131}} One study using crucian carp (''Carassius carassius'') found that HIF-1a increased in liver, gills and heart under hypoxia (0.7 mg l(-1) O2) at all temperatures (26, 18 and 8 degrees C). This study shows how HIF-1a is also upregulated under extreme temperature changes, HIF-1a increased in liver, gills and heart under the coldest treatment (8 degrees C) {{Cite journal |last=Rissanen |first=Eeva |last2=Tranberg |first2=Hanna K. |last3=Sollid |first3=Jørund |last4=Nilsson |first4=Göran E. |last5=Nikinmaa |first5=Mikko |date=2006-03-15 |title=Temperature regulates hypoxia-inducible factor-1 (HIF-1) in a poikilothermic vertebrate, crucian carp ( Carassius carassius ) |url=https://journals.biologists.com/jeb/article/209/6/994/16575/Temperature-regulates-hypoxia-inducible-factor-1 |journal=Journal of Experimental Biology |language=en |volume=209 |issue=6 |pages=994–1003 |doi=10.1242/jeb.02103 |issn=1477-9145}}

In an attempt to maintain homeostasis and compensate with hypoxic conditions, fish will upregulate HIF-1α and other stress related genes to handle the low oxygen codnitions. HIF-1α has been used in numerous studies to quantify the biochemical changes that occur within fish tissue before, during, and after hypoxia exposure. One study analyzing the effects of progressive hypoxia and reoxygenation in Korean Black rockfish (''Sebastes schlegelii''), showed that HIF-1a mRNA in gill and liver were significantly upregulated at loss of equilibrium (LOE) and 50% lethal time (LT50).{{Cite journal |last=Jia |first=Yudong |last2=Gao |first2=Yuntao |last3=Wan |first3=Jinming |last4=Gao |first4=Yunhong |last5=Li |first5=Juan |last6=Guan |first6=Changtao |date=2021-08-01 |title=Altered physiological response and gill histology in black rockfish, Sebastes schlegelii, during progressive hypoxia and reoxygenation |url=https://doi.org/10.1007/s10695-021-00970-5 |journal=Fish Physiology and Biochemistry |language=en |volume=47 |issue=4 |pages=1133–1147 |doi=10.1007/s10695-021-00970-5 |issn=1573-5168}} One study showed that flatfish turbot (''Scophthalmus maximus)'' increased gene expression in the hif pathway (hif-1α,hif-2α, hif-3α) under acute hypoxia as they attempted to compensate for the lack of DO in the environment. Flatfish are generally known to be more hypoxia tolerant and efficient at regulating low oxygenated environments than other fish. {{Cite journal |last1=Ma|first1=Qiang|last2=Xu|first2=Houguo|last3=Wei|first3=Yuliang|last4=Liang|first4=Mengqing|date=2024-02-01|title=Effects of acute hypoxia on nutrient metabolism and physiological function in turbot, Scophthalmus maximus|url=https://doi.org/10.1007/s10695-022-01154-5|journal=Fish Physiology and Biochemistry|language=en|volume=50|issue=1|pages=367–383|doi=10.1007/s10695-022-01154-5|pmid=36609890 |bibcode=2024FPBio..50..367M |issn=1573-5168}}{{Cite journal |last=Tunnicliffe |first=Verena |last2=Gasbarro |first2=Ryan |last3=Juanes |first3=Francis |last4=Qualley |first4=Jessica |last5=Soderberg |first5=Nicole |last6=Chu |first6=Jackson W. F. |date=2020-02 |title=An hypoxia‐tolerant flatfish: consequences of sustained stress on the slender sole Lyopsetta exilis (Pleuronectidae) in the context of a changing ocean |url=https://onlinelibrary.wiley.com/doi/10.1111/jfb.14212 |journal=Journal of Fish Biology |language=en |volume=96 |issue=2 |pages=394–407 |doi=10.1111/jfb.14212 |issn=0022-1112 |pmc=7028253 |pmid=31755100}} At the proteomic level, fat greenling (''Hexagrammos otakii)'', showed increased levels of HIF-1α protein when oxygen levels were 2.2 ± 0.2 DO mg/L for 6 hours, 12 hours, 24 hours, and at 48 hours, compared with the control group at 7.8 ± 0.2 DO mg/L using qRT-PCR and ELISA assays. Furthermore, HIF-1a was also correlated with hemoglobin (HB), ERO-1α, and lactic acid (LA) showing how it is involved with other metabolites {{Cite journal |last1=Zhan|first1=Yu|last2=Qi|first2=Xin|last3=Wu|first3=Yiting|last4=Gao|first4=Dongxu|last5=Zhao|first5=Ling|last6=Cao|first6=Shengnan|last7=Xue|first7=Zhuang|last8=Wang|first8=Wei|date=2024-12-01|title=Hypoxia-inducible factor-1α as a biomarker for individuals under hypoxia duration and pattern in fat greenling Hexagrammos otakii|url=https://www.sciencedirect.com/science/article/pii/S2352513424005477|journal=Aquaculture Reports|volume=39|article-number=102459|doi=10.1016/j.aqrep.2024.102459|bibcode=2024AqRep..3902459Z |issn=2352-5134}} However, this upregulation in HIF introduces energetic trade-offs that may inhibit other cellular functions such as mitochondrial oxygen consumption and disruption of the citric acid cycle. {{Cite journal |last1=Papandreou|first1=Ioanna|last2=Cairns|first2=Rob A.|last3=Fontana|first3=Lucrezia|last4=Lim|first4=Ai Lin|last5=Denko|first5=Nicholas C.|date=March 2006|title=HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption|url=https://linkinghub.elsevier.com/retrieve/pii/S155041310600060X|journal=Cell Metabolism|volume=3|issue=3|pages=187–197|doi=10.1016/j.cmet.2006.01.012|pmid=16517406 |issn=1550-4131}} One study using crucian carp (''Carassius carassius'') found that HIF-1a increased in liver, gills and heart under hypoxia (0.7 mg l(-1) O2) at all temperatures (26, 18 and 8 degrees C). This study shows how HIF-1a is also upregulated under extreme temperature changes, HIF-1a increased in liver, gills and heart under the coldest treatment (8 degrees C) {{Cite journal |last=Rissanen |first=Eeva |last2=Tranberg |first2=Hanna K. |last3=Sollid |first3=Jørund |last4=Nilsson |first4=Göran E. |last5=Nikinmaa |first5=Mikko |date=2006-03-15 |title=Temperature regulates hypoxia-inducible factor-1 (HIF-1) in a poikilothermic vertebrate, crucian carp ( Carassius carassius ) |url=https://journals.biologists.com/jeb/article/209/6/994/16575/Temperature-regulates-hypoxia-inducible-factor-1 |journal=Journal of Experimental Biology |language=en |volume=209 |issue=6 |pages=994–1003 |doi=10.1242/jeb.02103 |issn=1477-9145}}

=== HIF-1α in mammals and fish ===

=== HIF-1α in mammals and fish ===

HIF-1α in mammals and fish behave very similarly with both having the same amount of genes present and structure and function is virtually the same.{{Cite journal |last1=Shi|first1=Xiaowei|last2=Gao|first2=Feng|last3=Zhao|first3=Xianliang|last4=Pei|first4=Chao|last5=Zhu|first5=Lei|last6=Zhang|first6=Jie|last7=Li|first7=Chen|last8=Li|first8=Li|last9=Kong|first9=Xianghui|date=2023-12-01|title=Role of HIF in fish inflammation|url=https://www.sciencedirect.com/science/article/pii/S1050464823007088|journal=Fish & Shellfish Immunology|volume=143|article-number=109222|doi=10.1016/j.fsi.2023.109222|pmid=37956798 |bibcode=2023FSI...14309222S |issn=1050-4648}} However, the expression of HIF-1α differs within tissue type and species of fish, showing how specific isomers may differ in function with varying tissue types.{{Cite journal |last1=Rojas|first1=Diego A.|last2=Perez-Munizaga|first2=Daniela A.|last3=Centanin|first3=Lazaro|last4=Antonelli|first4=Marcelo|last5=Wappner|first5=Pablo|last6=Allende|first6=Miguel L.|last7=Reyes|first7=Ariel E.|date=2007-01-02|title=Cloning of hif-1α and hif-2α and mRNA expression pattern during development in zebrafish|url=https://www.sciencedirect.com/science/article/pii/S1567133X06001372|journal=Gene Expression Patterns|volume=7|issue=3|pages=339–345|doi=10.1016/j.modgep.2006.08.002|pmid=16997637 |issn=1567-133X}} Using ovoviviparous Korean Black rockfish (''Sebastes schlegelii'') in the Eastern Pacific, researchers found that hifα mRNA transcripts were upregulated during acute hypoxic stress. They also found that all of the motifs of the HIF proteins from mammalian species were present in Korean black rockfish and the rockfish had a shorter length of protein sequence than mammals.{{Cite journal |last1=Mu|first1=Weijie|last2=Wen|first2=Haishen|last3=Li|first3=Jifang|last4=He|first4=Feng|date=2015-09-01|title=HIFs genes expression and hematology indices responses to different oxygen treatments in an ovoviviparous teleost species Sebastes schlegelii|url=https://www.sciencedirect.com/science/article/pii/S014111361500063X|journal=Marine Environmental Research|volume=110|pages=142–151|doi=10.1016/j.marenvres.2015.04.008|pmid=26004518 |bibcode=2015MarER.110..142M |issn=0141-1136}}{{Cite journal |last1=Rahman|first1=Md. Saydur|last2=Thomas|first2=Peter|date=2007-07-15|title=Molecular cloning, characterization and expression of two hypoxia-inducible factor alpha subunits, HIF-1α and HIF-2α, in a hypoxia-tolerant marine teleost, Atlantic croaker (Micropogonias undulatus)|url=https://www.sciencedirect.com/science/article/pii/S0378111907001412|journal=Gene|volume=396|issue=2|pages=273–282|doi=10.1016/j.gene.2007.03.009|pmid=17467194 |issn=0378-1119}} Another study using bighead carp (''Aristichthys nobilis'') found that the tertiary structure of HIF-1α is very similar to that of mammalian mice.{{Cite journal |last1=Lin|first1=Yan|last2=Miao|first2=Ling-Hong|last3=Liu|first3=Bo|last4=Xi|first4=Bing-Wen|last5=Pan|first5=Liang-Kun|last6=Ge|first6=Xian-Ping|date=2021-04-01|title=Molecular cloning and functional characterization of the hypoxia-inducible factor-1α in bighead carp (Aristichthys nobilis)|url=https://doi.org/10.1007/s10695-020-00917-2|journal=Fish Physiology and Biochemistry|language=en|volume=47|issue=2|pages=351–364|doi=10.1007/s10695-020-00917-2|pmid=33474683 |bibcode=2021FPBio..47..351L |issn=1573-5168}}

HIF-1α in mammals and fish behave very similarly with both having the same amount of genes present and structure and function is virtually the same.{{Cite journal |last1=Shi|first1=Xiaowei|last2=Gao|first2=Feng|last3=Zhao|first3=Xianliang|last4=Pei|first4=Chao|last5=Zhu|first5=Lei|last6=Zhang|first6=Jie|last7=Li|first7=Chen|last8=Li|first8=Li|last9=Kong|first9=Xianghui|date=2023-12-01|title=Role of HIF in fish inflammation|url=https://www.sciencedirect.com/science/article/pii/S1050464823007088|journal=Fish & Shellfish Immunology|volume=143|article-number=109222|doi=10.1016/j.fsi.2023.109222|pmid=37956798 |bibcode=2023FSI...14309222S |issn=1050-4648}} However, the expression of HIF-1α differs within tissue type and species of fish, showing how specific isomers may differ in function with varying tissue types.{{Cite journal |last1=Rojas|first1=Diego A.|last2=Perez-Munizaga|first2=Daniela A.|last3=Centanin|first3=Lazaro|last4=Antonelli|first4=Marcelo|last5=Wappner|first5=Pablo|last6=Allende|first6=Miguel L.|last7=Reyes|first7=Ariel E.|date=2007-01-02|title=Cloning of hif-1α and hif-2α and mRNA expression pattern during development in zebrafish|url=https://www.sciencedirect.com/science/article/pii/S1567133X06001372|journal=Gene Expression Patterns|volume=7|issue=3|pages=339–345|doi=10.1016/j.modgep.2006.08.002|pmid=16997637 |issn=1567-133X}} Using [[Ovoviviparity|ovoviviparous]] Korean Black rockfish (''Sebastes schlegelii'') in the Eastern Pacific, researchers found that HIFa pathway mRNA transcripts were upregulated during acute hypoxic stress. They also found that all of the motifs of the HIF proteins from mammalian species were present in Korean black rockfish and the rockfish had a shorter length of protein sequence than mammals.{{Cite journal |last1=Mu|first1=Weijie|last2=Wen|first2=Haishen|last3=Li|first3=Jifang|last4=He|first4=Feng|date=2015-09-01|title=HIFs genes expression and hematology indices responses to different oxygen treatments in an ovoviviparous teleost species Sebastes schlegelii|url=https://www.sciencedirect.com/science/article/pii/S014111361500063X|journal=Marine Environmental Research|volume=110|pages=142–151|doi=10.1016/j.marenvres.2015.04.008|pmid=26004518 |bibcode=2015MarER.110..142M |issn=0141-1136}}{{Cite journal |last1=Rahman|first1=Md. Saydur|last2=Thomas|first2=Peter|date=2007-07-15|title=Molecular cloning, characterization and expression of two hypoxia-inducible factor alpha subunits, HIF-1α and HIF-2α, in a hypoxia-tolerant marine teleost, Atlantic croaker (Micropogonias undulatus)|url=https://www.sciencedirect.com/science/article/pii/S0378111907001412|journal=Gene|volume=396|issue=2|pages=273–282|doi=10.1016/j.gene.2007.03.009|pmid=17467194 |issn=0378-1119}} Another study using bighead carp (''Aristichthys nobilis'') found that the tertiary structure of HIF-1α is very similar to that of mammalian mice showing that mice and fish HIF-1a levels may be comparable in future studies.{{Cite journal |last1=Lin|first1=Yan|last2=Miao|first2=Ling-Hong|last3=Liu|first3=Bo|last4=Xi|first4=Bing-Wen|last5=Pan|first5=Liang-Kun|last6=Ge|first6=Xian-Ping|date=2021-04-01|title=Molecular cloning and functional characterization of the hypoxia-inducible factor-1α in bighead carp (Aristichthys nobilis)|url=https://doi.org/10.1007/s10695-020-00917-2|journal=Fish Physiology and Biochemistry|language=en|volume=47|issue=2|pages=351–364|doi=10.1007/s10695-020-00917-2|pmid=33474683 |bibcode=2021FPBio..47..351L |issn=1573-5168}}

=== HIF-1α quantification ===

=== HIF-1α quantification ===