[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

Ammonia toxicity in fish

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2002.36088

Ursodeoxycholic acid in cholestatic liver disease: Mechanisms of action and therapeutic use revisited

The ureogenic potential of five species of freshwater, air-breathing teleosts was studied. The activity of all five enzymes of the ornithine-urea (c-u) cycle could be assayed in four out of the five species. The enzymatic activities were generally high. Physiological levels of ammonia and urea and of enzymes of the o-u cycle have been considered to be associated with the potential for terrestrial life in different species. The species having an efficient o-u cycle had low levels of ammonia and high levels of urea in various tissues. Ammonia was the major excretory product in the aquatic medium in all five air-breathing species. However, the rate of excretion of urea was greater than that of exclusively freshwater teleosts reported earlier. There was apparently no diurnal variation in the rates of excretion of ammonia. The rate of excretion of urea was significantly higher during the night than during the day in only two of the species examined, namely, Heteropneustes fossilis and Anabas testudineus. These observations strengthen our earlier suggestion that active ureogenesis through a functional o-u cycle does exist in some freshwater, air-breathing teleosts.

Comparative study of ureogenesis in freshwater, air-breathing teleosts

The interaction between cell volume and taurocholate excretion into bile was studied in isolated perfused rat liver. Cell swelling due to hypo-osmotic exposure, addition of amino acids or insulin stimulated taurocholate excretion into bile and bile flow, whereas hyperosmotic cell shrinkage inhibited these. These effects were explained by changes in Vmax of taurocholate excretion into bile: Vmax. increased from about 300 to 700 nmol/min per g after cell swelling by 12-15% caused by either hypo-osmotic exposure or addition of amino acids under normo-osmotic conditions. Steady-state taurocholate excretion into bile was not affected when the influent K+ concentration was increased from 6 to 46 mM or decreased to 1 mM with iso-osmoticity being maintained by corresponding changes in the influent Na+ concentration. Replacement of 40 mM-NaCl by 80 mM-sucrose decreased taurocholate excretion into bile by about 70%; subsequent hypo-osmotic exposure by omission of sucrose increased taurocholate excretion to 160%. Only minor, statistically insignificant, effects of aniso-osmotic cell volume changes on the appearance of bolus-injected horseradish peroxidase in bile were observed. Taurocholate (400 microM) exhibited a cholestatic effect during hyperosmotic cell shrinkage, but not during hypo-osmotic cell swelling. Both taurocholate and tauroursodeoxycholate increased liver cell volume. Tauroursodeoxycholate stimulated taurocholate (100 microM) excretion into bile. This stimulatory effect was strongly dependent on the extent of tauroursodeoxycholate-induced cell swelling. During continuous infusion of taurocholate (100 microM) further addition of tauroursodeoxycholate at concentrations of 20, 50 and 100 microM increased cell volume by 10, 8 and 2% respectively, in parallel with a stimulation of taurocholate excretion into bile by 29, 27 and 9% respectively. There was a close relationship between the extent of cell volume changes and taurocholate excretion into bile, regardless of whether cell volume was modified by tauroursodeoxycholate, amino acids or aniso-osmotic exposure. The data suggest that: (i) liver cell volume is one important factor determining bile flow and biliary taurocholate excretion; (ii) swelling-induced stimulation of taurocholate excretion into bile is probably not explained by alterations of the membrane potential; (iii) bile acids modulate liver cell volume; (iv) taurocholate-induced cholestasis may depend on cell volume; (v) stimulation of taurocholate excretion into bile by tauroursodeoxycholate can largely be explained by tauroursodeoxycholate-induced cell swelling.

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Cell volume and bile acid excretion

An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Haussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane.

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.

Activities of all the enzymes of ornithine-urea (o-u) cycle and uricolytic pathway were assayed in different tissues of a freshwater air-breathing teleost, Heteropneustes fossilis. High activity of all o-u cycle enzymes as observed in the liver and kidney, were comparable to those of actively ureogenic fishes and amphibians. All the three enzymes of uricolytic pathway were found only in liver tissue. These observations strengthen an earlier suggestion made that active ureogenesis did exist in some freshwater teleosts such as H. fossilis. Presence of an active o-u cycle in H. fossilis indicates that this fish is either relatively primitive to the purely aquatic freshwater teleosts retaining the ancestral character of a functional o-u cycle or the genes for the synthesis of o-u cycle enzymes might have been derepressed as a secondary modification for its adaptation to temporary dehydration or hyper-ammonia environment.

Active ureogenesis in a freshwater air‐breathing teleost, Heteropneustes fossilis

Most of the Indian air-breathing teleosts are primarily ammoniotelic, but appear to have retained the genes for the urea cycle enzymes, since a full complement of urea cycle enzymes have been reported for many of them. The ability to synthesize urea by these fish is probably due to their amphibious nature, and their normal habitat of swamps, where the water ammonia level may to be quite high, is uninhabitable to any typical freshwater teleosts. One of these air-breathing species, the singhi catfish ( Heteropneustes fossilis ), can tolerate very high ambient total ammonia concentrations (up to 75 mM ammonium chloride) for weeks without any deleterious effects. Transition from ammoniotelism to ureotelism occurs in some of these species of air-breathing fish when exposed to apparently stressful conditions such as higher ambient ammonia, to air, and also when they live in semidry condition inside mud during habitat drying. Although the real mechanism(s) of regulation of ureogenesis is not clear in these fish, given available data, it is hypothesized that the accumulation of ammonia within the body per se under the above stressful conditions is likely the internal modulator for enhanced ureogenesis mainly to avoid any build up of ammonia to a level that can be toxic to these fish. An active urea cycle is believed to predominate over uricolysis as a source of urea, even though both pathways are present in these air-breathing fish. The presence of significant levels of both carbamyl phosphate synthetase (CPS), CPS I-like and CPS III activities, reported in some air-breathing catfishes, may represent intermediate scenarios for a proposed evolutionary transition from CPS III to CPS I, or may play an important physiological adaptive role in the tolerance of these fish to high concentrations of ambient ammonia

Nirmalendu Saha

Papers

Comparative study of ureogenesis in freshwater, air-breathing teleosts

Cell volume and bile acid excretion

Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.

Active ureogenesis in a freshwater air‐breathing teleost, Heteropneustes fossilis

Ureogenesis in Indian air-breathing teleosts: adaptation to environmental constraints