Ip Yuen Kwong, Alex
Lab: Molecular and Environmental Physiology Laboratory (S1A 05-22.)
Strategies adopted by air-breathing fishes to defend against ammonia toxicity during aerial exposure.
Fishes currently being studied include the mudskippers (Periophthalmodon schlosseri, Boleophthalmus boddaerti, and Periophthalmus chrysospilos), the marble goby (Oxyeleotris marmoratus), the four-eyed sleeper (Bostrichythes sinensis), the snakeheads (Channa asiatica and Channa micropeltes), the Oriental weather loach (Misgurnus anguillicaudatus), the African sharptooth catfish (Clarias gariepinus) and the swamp eel (Monopterus albus). Liver failure in mammals leads to hepatic encephalopathy manifested as comma followed by death. It is hoped that results obtained will reveal adaptations involved in conferring these air-breathing fishes high ammonia-tolerance, which can be of value for the formulation of treatments for patients with liver failure. At present, efforts are focused on (1) the role of glutamine synthetase in ammonia detoxification and how it can be up-regulated in response to an ammonia surge, and (2) active transport of NH4+ and H+ excretion via V-type H+-ATPase.
Urea synthesis and the ornithine-urea cycle.
Animals currently being studied include the giant African snail (Achatina fulica), the Asian freshwater stingray (Himantura signifer), the South American stingray (Potamotrygon motoro), the marine blue-spotted stingray (Taeniura lymma), the African lungfishes (Protopterus dolloi, Protopterus aethiopicus and Protopterus annectens), the Chinese fire-belly newt (Cynops orientalis), the crab-eating frog (Rana cancrivora), and the soft-shelled turtle (Amyda cartilaginea). Mammals detoxify ammonia to urea. However, whether the usurpation of the arginine synthetic pathway for urea production was directed to ammonia detoxification or osmotic retention of water is a moot point. Attempts are made in my laboratory to elucidate the role of urea synthesis in various animals during emersion, exposure to environmental ammonia, injection/infusion with ammonia or feeding. We aim to elucidate how the ornithine-urea cycle capacity of these animals can be up-regulated under certain environmental conditions.
Ammonia toxicity to brains of vertebrates.
Fish currently being studied are those which had extraordinary capacity to synthesize and accumulate glutamine and/or to tolerate high levels of ammonia in their brains. These include the mudskippers, the swamp eel and the African catfish. Specifically we focus on (1) the deleterious effects of glutamine synthesis and accumulation and (2) glutamate dysfunction leading to activation of the N-methyl-D-aspartate (NMDA) type glutamate receptor, using pharmacological agents like MK-801 and MSO. I am interested in finding out why, unlike mammals, some of these unique fishes have very high tolerance of ammonia in their brains, and how ammonia toxicity to mammalian brains can be ameliorated.
Metabolic rate reduction in aestivating African lungfishes and swamp eel.
Lungfishes (or dipnoans as they are “dual breathers”) are an archaic group of fishes, characterized by the possession of a lung opening off the ventral side of the oesophagus. The African lungfishes (Protopterus aethiopicus, Protopterus annectens, Protopterus amphibious and Protopterus dolloi) can aestivate in subterranean mud cocoons for long periods of time (up to 5 years). On the other hand, the swamp eel can aestivate in mud without forming a cocoon for months during drought. I am interested in (a) how dehydration is avoided, (b) how metabolic rate is reduced to prevent exhaustion of internal reserves, and (c) how the pollution of the internal environment is ameliorated. Answers to all these questions have important biomedical implications.
Ip, Y. K., and Chew, S. F. (2010). Ammonia production, excretion, toxicity, and defense in fish: a review. Front. Physio. 1:134. Doi: 10.3389/fphy.2010.00134.
Chew, S. F., Tng, Y. Y. M., Wee, N, L. J., Tok, C. Y., Wilson, J. M., and Ip, Y. K. (2010). Intestinal osmoregulatory acclimation and nitrogen metabolism in juveniles of the freshwater marble goby exposed to seawater. J. Comp. Physiol. B 180, 511-520.
Moreira-Silva, J.; Tsui, T. K. N.; Coimbra, J.; Vijayan, M. M.; Ip, Y. K.; Wilson, J. M. (2010) Branchial ammonia excretion in the Asian weatherloach Misgurnus anguillicaudatus. Comparative biochemistry and physiology. Toxicology & pharmacology 151:40-50.
Ip, Y. K. and Chew, S. F. “Nitrogen metabolism and excretion during aestivation” Chapter 4, p. 63-94, in Aestivation, Molecular and Physiology Aspects (eds. C. A Navas and J. E. Carvalho), Springer-Verlag, (2010) Germany, Berline Heidelberg.
Frick, N. T., Bystriansky, J. S., Ip, Y. K., Chew, S. F. and Ballantyne, J. S. Cytochrome c oxidase is regulated by modulations in protein expression and mitochondrial membrane phospholipid composition in estivating African lungfish. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology 298 (2010): R608-R616.
Peh, W. Y. X., Chew, S. F., Ching, B., and Ip, Y. K. Roles of intestinal glutamate dehydrogenase and glutamine synthetase in environmental ammonia detoxification in the euryhaline four-eyed sleeper, Bostrychus sinensis. Aquatic Toxicology 98 (2010): 91-98.
Icardo, J. M., Wong, W. P., Colvee, E., Loong, A. M. and Ip, Y. K. The anatomy of the gastrointestinal tract of the African lungfish, Protopterus annectens. The Anatomical Record 293 (2010): 1146-1154.
Evans, D. H., Axelsson, M., Beltz, B., Burggren, W., Castellini, M., Clements, K.D., Crockett, L., Gilmour, K. M., Henry, R. P., Hirose, S., Ip, A. Y., Londraville, R., Lucu, C., Poertner, H. O., Summers, A. and Wright, P. (2010) Frontiers in Aquatic Physiology - grand challenge. Front. Physio. 1:6. doi:10.3389/fphys.2010.00006
Icardo, J. M., Wong, W. P., Colvee, E., Garofalo, F., Loong, A. M. and Ip, Y. K. (2011). The gut of the juvenile African lungfish Protopterus annectens: A light and scanning electron microscope study. Journal of Morphology 272: 769-779.
Giusi, G., Crudo, M., Vito, A. D., Facciolo, R. M., Garofalo, F., Chew, S. F., Ip, Y. K., and Canoaca, M. (2011). Lungfish aestivating activities are locked in distinct encephalic ɣ-aminobutyric acid type A receptor α subunits. Journal of Neuroscience Research 89: 418-428.
Tok, C. Y., Chew, S. F. and Ip, Y. K. (2011) Gene cloning and mRNA expression of glutamate dehydrogenase in the liver, brain, and intestine of the swamp eel, Monopterus albus (Zuiew), exposed to freshwater, terrestrial conditions, environmental ammonia, or salinity stress. Front. Physio. 2:100. doi:10.3389/fphys.2011.00100
Icardo, J., Loong, A. M., Colvee, W., Wong, W. P. and Y. K. Ip (2012) The alimentary canal of the African lungfish Protopterus annectens during aestivation and after arousal. Anatomical Record 295:60-72.
Loong, A. M., Hiong, K. C., Wong, W. P., Chew, S. F., and Ip, Y. K. (2012). Differential gene expression in the liver of the African lungfish, Protopterus annectens, after 6 days of aestivation in air. J. Comp. Physiol. B 182: 231-245
Loong, A. M., Chng, Y. R., Chew, S. F., Wong, W. P., and Ip, Y. K. (2012). Molecular characterization and mRNA expression of carbamoyl phosphate synthetase III in the liver of the African lungfish, Protopterus annectens, during aestivation or exposure to ammonia. J. Comp. Physiol. B In press.
Loong, A. M., Chew, S. F., Wong, W. P., Lam, S. H., and Ip, Y. K. (2012). Both seawater acclimation and environmental ammonia exposure lead to increases in mRNA expression and protein abundance of Na+:K+:2Cl- cotransporter in the gills of the climbing perch, Anabas testudineus. J. Comp. Physiol. B In press.
Ip, Y. K., Wilson, J. M., Loong, A. M., Chen, X. L., Wong, W. P., Lam, S. H. and Chew, S. F. (2012) Cystic fibrosis transmembrane conductance regulator-like Cl− channel in the gills of the climbing perch, Anabas testudineus, is involved in both hypoosmotic regulation during seawater acclimation and active ammonia excretion during ammonia exposure. J Comp Physiol B Submitted and under revision.
Ip, Y. K., Loong, A. M., Kuah, J. S., Sim, E. W. L. Chen, X. L., Wong, W. P., Lam, S. H., Wilson, J. M. and Chew, S. F. (2012) The roles of three branchial Na+/K+-ATPase α-subunit isoforms in freshwater adaptation, seawater acclimation and active ammonia excretion in Anabas testudineus. Am. J. Physiol Submitted and under revision.