PUBLICATION
The zebrafish Cytochrome b5/Cytochrome b5 reductase/NADH system efficiently reduces Cytoglobins 1 and 2 - Conserved activity of Cytochrome b5/Cytochrome b5 reductases during vertebrate evolution
- Authors
- Amdahl, M.B., Petersen, E.E., Bocian, K.A., Kaliszuk, S.J., DeMartino, A.W., Tiwari, S., Sparacino-Watkins, C.E., Corti, P., Rose, J.J., Gladwin, M.T., Fago, A., Tejero, J.
- ID
- ZDB-PUB-190702-2
- Date
- 2019
- Source
- Biochemistry 58(29): 3212-3223 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Biological Evolution*
- Cytochrome-B(5) Reductase/genetics
- Cytochrome-B(5) Reductase/metabolism*
- Cytochromes b5/genetics
- Cytochromes b5/metabolism*
- Cytoglobin/genetics
- Cytoglobin/metabolism*
- Enzyme Activation/physiology
- NAD/genetics
- NAD/metabolism*
- Protein Binding/physiology
- Zebrafish
- PubMed
- 31257865 Full text @ Biochemistry
Citation
Amdahl, M.B., Petersen, E.E., Bocian, K.A., Kaliszuk, S.J., DeMartino, A.W., Tiwari, S., Sparacino-Watkins, C.E., Corti, P., Rose, J.J., Gladwin, M.T., Fago, A., Tejero, J. (2019) The zebrafish Cytochrome b5/Cytochrome b5 reductase/NADH system efficiently reduces Cytoglobins 1 and 2 - Conserved activity of Cytochrome b5/Cytochrome b5 reductases during vertebrate evolution. Biochemistry. 58(29):3212-3223.
Abstract
Cytoglobin is a heme protein evolutionarily related to hemoglobin and myoglobin. Cytoglobin is expressed ubiquitously in mammalian tissues; however its physiological functions are yet unclear. Phylogenetic analyses indicate that the cytoglobin gene is highly conserved in vertebrate clades, from fish to reptiles, amphibians, birds, and mammals. Most proposed roles for cytoglobin require the maintenance of a pool of reduced cytoglobin (FeII). We have shown previously that the human cytochrome b5 / cytochrome b5 reductase system, considered a quintessential hemoglobin/myoglobin reductant, can reduce human and zebrafish cytoglobins up to 250-fold faster than human hemoglobin or myoglobin. It was unclear whether this reduction of zebrafish cytoglobins by mammalian proteins indicates a conserved pathway through vertebrate evolution. Here we report the reduction of zebrafish cytoglobins 1 and 2 by the zebrafish cytochrome b5 reductase and the two zebrafish cytochrome b5 isoforms. In addition, the reducing system also supports reduction of Globin X, a conserved globin in fish and amphibians. Indeed, the zebrafish reducing system can maintain a fully reduced pool for both cytoglobins, and both cytochrome b5 isoforms can support this process. We determined the P50 for oxygen being 0.5 torr for cytoglobin-1 and 4.4 torr for cytoglobin-2 at 25 °C. Thus, even at low oxygen tension, the reduced cytoglobins may exist in a predominant oxygen-bound form. In these conditions, the cytochrome b5/cytochrome b5 reductase system can support a conserved role for cytoglobins through evolution, providing electrons for redox signaling reactions such as nitric oxide dioxygenation, nitrite reduction or phospholipid oxidation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping