Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation in fish

Abstract

Gas transport concepts in vertebrates have naturally been formulated based on human blood. However, the first vertebrates were aquatic, and fish and tetrapods diverged hundreds of millions years ago. Water-breathing vertebrates live in an environment with low and variable O 2 levels, making environmental O 2 an important evolutionary selection pressure in fishes, and various features of their gas transport differ from humans. Erythrocyte function in fish is of current interest, because current environmental changes affect gas transport, and because especially zebrafish is used as a model in biomedical studies, making it important to understand the differences in gas transport between fish and mammals to be able to carry out meaningful studies. Of the close to thirty thousand fish species, teleosts are the most species-numerous group.However, two additional radiations are discussed: agnathans and elasmobranchs.The gas transport by elasmobranchs may be closest to the ancestors of tetrapods. The major difference in their haemoglobin (Hb) function to humans is their high urea tolerance. Agnathans differ from other vertebrates by having Hbs, where cooperativity is achieved by monomer-oligomer equilibria. Their erythrocytes also lack the anion exchange pathway with profound effects on CO 2 transport. Teleosts are characterized by highly pH sensitive Hbs, which can fail to become fully O 2 -saturated at low pH. An adrenergically stimulated Na + /H + exchanger has evolved in their erythrocyte membrane, and plasma-accessible carbonic anhydrase can be differentially distributed among their tissues. Together, and differing from other vertebrates, these features can maximize O 2 unloading in muscle while ensuring O 2 loading in gills. K E Y W O R D Sadrenergically stimulated Na + /H + exchange, anion exchange, Bohr effect, carbonic anhydrase, erythrocyte, oxygen equilibrium curve (OEC), Root effect 2 of 16 | NIKINMAA et Al.3 40 ) stabilize the T-state (these so-called allosteric effectors bind to sites other than the O 2 binding site). The overall OEC of Hb molecules is determined by the probabilities of T-or R-state occurrence; the equilibrium between T-and R-states is virtually instantaneous.F I G U R E 4 O 2 equilibrium curves of rainbow trout (A) at resting plasma pH (7.65) and (B) at pH 7.40, where the Root effect has been induced (ie, O 2 saturation approaches asymptotically a value below full saturation, in this case maximal O 2 saturation is 69%, ie, Root effect 31%; data from 98 )

Mechanism Study of the Protective Effects of Sodium Tanshinone IIA Sulfonate Against Atorvastatin-Induced Cerebral Hemorrhage in Zebrafish: Transcriptome Analysis

“…As shown in Figure 3 , the cellular processes related to oxygen metabolism and exchange were most involved in the protective effect of STS against cerebral hemorrhage. Hemoglobin and carbonic anhydrase are essential for transportation and exchange of CO 2 and O 2 in red blood cells ( Nikinmaa et al, 2019 ). Carbonic anhydrase accompanied by Na+/H+ exchange regulates intracellular PH ( Parks et al, 2017 ).…”

“…The expression levels of genes of interest, which encode hemoglobin, Na+/H+ exchanger, and carbonic anhydrase, were verified by real-time PCR analysis. Hemoglobin proteins caused dramatic neuronal toxicity in cerebral hemorrhage and regulated the oxygen and carbon dioxide exchange with carbonic anhydrase in blood cells ( Hostettler et al, 2019 ; Nikinmaa et al, 2019 ). We found that the mRNA expression levels of hemoglobin ( hbae1.3, hbae3, hbae5, hbbe2 and hbbe3 ), Na+/H+ exchanger ( slc4a1a and slc9a1 ), and carbonic anhydrase ( cahz ) genes were significantly elevated after cerebral hemorrhage, while STS alleviated the expression changes in of these genes ( Figure 4 ).…”

The evolution of red blood cell shape in fishes

“…Differently from mammals, fish RBCs are nucleated cells and have many cytoplasmic organelles, such as mitochondria, Golgi complex, centrioles, ribosomes, microtubules, rough and smooth endoplasmic reticulum (Sekhon & Beams, 1969), and a range of cytoplasmatic enzymes involved in the anaerobic glycolysis (Sephton et al., 1991). These organelles and enzymes allow the functions of RBC to be finely regulated and somewhat independent from other components of the haematopoietic system, enabling fish to occupy a wide range of environments (Nikinmaa et al., 2019). Therefore, species may respond rapidly to changes in oxygen availability (Witeska, 2013), which indicates that it is not constrained by inheritance (Arnold, 1992) or phylogenetic inertia, at least to a certain degree.…”

The evolution of red blood cell shape in a continental radiation of fishes

“…Differently from mammals, fish RBC are nucleated cells and have many cytoplasmic organelles, such as mitochondria, Golgi complex, centrioles, ribosomes, microtubules, rough and smooth endoplasmic reticulum (Sekhon and Beams 1969), as well as a range of cytoplasmatic enzymes involved in the anaerobic glycolysis (Sephton et al 1991). These organelles and enzymes allow the functions of RBC to be finely regulated and somewhat independent from other components of the hematopoietic system, enabling fish to occupy a wide range of environments (Nikinmaa et al 2019). Therefore, species may respond rapidly to changes in oxygen availability (Witeska, 2013), which indicates that it is not constrained by inheritance (Arnold 1992) or phylogenetic inertia, at least to a certain degree.…”