0000000000038507
AUTHOR
Frank Gerlach
Duplicated cytoglobin genes in teleost fishes
Cytoglobin is a recently discovered myoglobin-related O2-binding protein of vertebrates with uncertain function. It occurs as single-copy gene in mammals. Here, we demonstrate the presence of two paralogous cytoglobin genes (Cygb-1 and Cygb-2) in the teleost fishes Danio rerio, Oryzias latipes, Tetraodon nigroviridis, and Takifugu rubripes. The globin-typical introns at positions B12.2 and G7.0 are conserved in both genes, whereas the C-terminal exon found in mammalian cytoglobin is absent in the fish genes. Phylogenetic analyses show that the two cytoglobin genes diverged early in teleost evolution. This is confirmed by gene synteny analyses, which suggest a large-scale duplication event. …
Neuroglobin and cytoglobin in search of their role in the vertebrate globin family
Neuroglobin and cytoglobin are two recent additions to the family of heme-containing respiratory proteins of man and other vertebrates. Here, we review the present state of knowledge of the structures, ligand binding kinetics, evolution and expression patterns of these two proteins. These data provide a first glimpse into the possible physiological roles of these globins in the animal's metabolism. Both, neuroglobin and cytoglobin are structurally similar to myoglobin, although they contain distinct cavities that may be instrumental in ligand binding. Kinetic and structural studies show that neuroglobin and cytoglobin belong to the class of hexa-coordinated globins with a biphasic ligand-bi…
Coping with cyclic oxygen availability: evolutionary aspects
Both the gradual rise in atmospheric oxygen over the Proterozoic Eon as well as episodic fluctuations in oxygen over several million-year time spans during the Phanerozoic Era, have arguably exerted strong selective forces on cellular and organismic respiratory specialization and evolution. The rise in atmospheric oxygen, some 2 billion years after the origin of life, dramatically altered cell biology and set the stage for the appearance of multicelluar life forms in the Vendian (Ediacaran) Period of the Neoproterozoic Era. Over much of the Paleozoic, the level of oxygen in the atmosphere was near the present atmospheric level (21%). In the Late Paleozoic, however, there were extended times…
Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia.
Cytoglobin is a recently discovered vertebrate globin distantly related to myoglobin, and its function is unknown. Here we present the first detailed analysis of the distribution and expression of cytoglobin. Northern and Western blotting experiments show the presence of cytoglobin mRNA and protein in a broad range of tissues. Quantitative PCR demonstrates an up-regulation of cytoglobin mRNA levels in rat heart and liver under hypoxic conditions (22 and 44 h of 9% oxygen). Immunofluorescence studies with three antibodies directed against different epitopes of the protein consistently show cytoglobin in connective tissue fibroblasts as well as in hepatic stellate cells. Cytoglobin is also pr…
Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax.
The subterranean mole rat Spalax is an excellent model for studying adaptation of a mammal toward chronic environmental hypoxia. Neuroglobin (Ngb) and cytoglobin (Cygb) are O 2 -binding respiratory proteins and thus candidates for being involved in molecular hypoxia adaptations of Spalax . Ngb is expressed primarily in vertebrate nerves, whereas Cygb is found in extracellular matrix-producing cells and in some neurons. The physiological functions of both proteins are not fully understood but discussed with regard to O 2 supply, the detoxification of reactive oxygen or nitrogen species, and apoptosis protection. Spalax Ngb and Cygb coding sequences are strongly conserved. However, mRNA and …
A Membrane-Bound Vertebrate Globin
The family of vertebrate globins includes hemoglobin, myoglobin, and other O(2)-binding proteins of yet unclear functions. Among these, globin X is restricted to fish and amphibians. Zebrafish (Danio rerio) globin X is expressed at low levels in neurons of the central nervous system and appears to be associated with the sensory system. The protein harbors a unique N-terminal extension with putative N-myristoylation and S-palmitoylation sites, suggesting membrane-association. Intracellular localization and transport of globin X was studied in 3T3 cells employing green fluorescence protein fusion constructs. Both myristoylation and palmitoylation sites are required for correct targeting and m…
Regulation and Role of Neuroglobin and Cytoglobin Under Hypoxia
Neuroglobin (Ngb) and cytoglobin (Cygb) are two novel members of the globin superfamily that are ubiquitously present in vertebrates. Their exact physiological roles are still uncertain. Here we review the expression of Ngb and Cygb, with particular emphasis on their regulation and potential role under hypoxia. Ngb expression is confined to neurons and some endocrine tissues. At the subcellular level, Ngb is associated with the presence of mitochondria and thus linked to the oxidative metabolism. Hypoxia or ischemic insults most likely do not strongly increase Ngb levels in the rodent brain. This might be explained by the fact that most mammals are not adapted to low oxygen levels. In zebra…
Cerebral expression of neuroglobin and cytoglobin after deep hypothermic circulatory arrest in neonatal piglets
Deep hypothermic circulatory arrest (DHCA) is used in corrective cardiac surgery for complex congenital heart disease. Endogenous protective mechanisms may be responsible for the prevention of brain damage after hypothermic ischemia. Neuroglobin and cytoglobin are expressed in brain cells and appear to modulate hypoxic-ischemic brain injury. However, their neuroprotective potency is still not understood. Thus the aim of this study was to detect the influence exerted by DHCA on their expression.The effects of DHCA were analyzed in a neonatal piglet model with cardiopulmonary bypass, DHCA of 60 and 120 min and subsequent reperfusion of 6h. Complete histological analysis and changes in the mRN…
Oxygen-induced changes in hemoglobin expression in Drosophila
The hemoglobin gene 1 (dmeglob1) of the fruit fly Drosophila melanogaster is expressed in the tracheal system and fat body, and has been implicated in hypoxia resistance. Here we investigate the expression levels of dmeglob1 and lactate dehydrogenase (a positive control) in embryos, third instar larvae and adult flies under various regimes of hypoxia and hyperoxia. As expected, mRNA levels of lactate dehydrogenase increased under hypoxia. We show that expression levels of dmeglob1 are decreased under both short- and long-term hypoxia, compared with the normoxic (21% O2) control. By contrast, a hypoxia/reoxygenation regime applied to third instar larvae elevated the level of dmeglob1 mRNA. A…
Genomic Organization and Molecular Evolution of the Genes for Neuroglobin and Cytoglobin in the Hypoxiatolerant Israeli Mole Rat, Spalax Carmeli
The genes for the two respiratory proteins neuroglobin (Ngb) and cytoglobin (Cygb) in the subterranean Israeli mole rat Spalax carmeli have been sequenced and compared to other mammals including human. Coding regions of both Spalax genes are highly conserved on the nucleotide and amino acid level. The ratios of non-synonymous to synonymous nucleotide substitutions suggest strong purifying selection acting on Ngb and Cygb in all mammals. Thus, there appears to be no special sequence level adaptation in the two respiratory proteins within the hypoxia-tolerant mole rat. On the genomic level, Spalax Ngb and Cygb gene regions revealed the conserved 4-exon-3-intron structure and conserved CpG-ric…
Oxygen Supply from the Bird's Eye Perspective
The visual process in the vertebrate eye requires high amounts of metabolic energy and thus oxygen. Oxygen supply of the avian retina is a challenging task because birds have large eyes, thick retinae, and high metabolic rates but neither deep retinal nor superficial capillaries. Respiratory proteins such as myoglobin may enhance oxygen supply to certain tissues, and thus the mammalian retina harbors high amounts of neuroglobin. Globin E (GbE) was recently identified as an eye-specific globin of chicken (Gallus gallus). Orthologous GbE genes were found in zebra finch and turkey genomes but appear to be absent in non-avian vertebrate classes. Analyses of globin phylogeny and gene synteny sho…
Genomic response of the rat brain to global ischemia and reperfusion
To identify genes that are involved in ischemia response of the brain, we have evaluated changes of gene expression in rat cerebrum after 15 min complete global ischemia, followed by reperfusion for 1 h, 6 h or 24 h. The expression profiles of approximately 30,000 transcripts from three subjects in each group (including sham-operated controls) were monitored employing oligonucleotide microarrays. About 20,000 transcripts were detectable in rat brains. The levels of 576 transcripts (approximately 2.9%) were significantly altered in response to experimental ischemia. 419 transcripts were up- and 157 downregulated; 39 transcripts changed after 1 h reperfusion, 174 after 6 h and 462 after 24 h.…