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.
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 182:367–379.
Loong, A. M., Chew, S. F., Wong, W. P., Lam, S. H., 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 freshwater climbing perch, Anabas testudineus. J. Comp. Physiol. B 182: 491-506.
Ip, Y. K., Loong, A. M., Kuah, J. S., Sim, E. W. L., Chen, X. L., Wong, W. P., Lam, S. H., Delgado, I. L. S., Wilson, J. M., 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. Regul. Integr. Comp. Physiol. 303:R112-R125.
Ip, Y. K., Wilson, J. M., Loong, A. M., Chen, X. L., Wong, W. P., Delgado, I. L. S., Lam, S. H., Chew, S. F. (2012). Cystic fibrosis transmembrane conductance regulator-like Cl− channel in the gills of the climbing perch, Anabas testudineus, isinvolved in both hypoosmotic regulation during seawater acclimation and active ammonia excretion during ammonia exposure. J. Comp. Physiol. B 182:793–812
Giusi, G., Zizza, M., Facciolo, R. M., Chew, S. F., Ip, Y. K., Canonaco, M. (2012). Aestivation and hypoxia-related events share common silent neuron trafficking processes. BMC Neurosci. 2012 13(1):39.
Icardo, J. M., Wong, W. P., Colvee, E., Loong, A. M., Ip, Y. K. (2012). The spleen of the African lungfish Protopterus annectens: freshwater and aestivation. Cell Tissue Res. 350: 143-156.
Ip, Y. K., Loong, A. M., Chng, Y. R., Hiong, K. C., Chew, S. F. (2012).Hepatic carbamoyl phosphate synthetase (CPS) I and urea contents in the hylid tree frog, Litoria caerulea: transition from CPS III to CPS I. J Comp Physiol B. 182: 1087-1094.
Ip, Y. K., Loong, A. M., Lee, S. L. M., Ong, J. L. Y., Wong, W. P and Chew, S. F. (2012). The Chinese soft-shelled turtle, Pelodiscus sinensis, excretes urea mainly through the mouth instead of the kidney. J. Exp. Biol.215: 3732-3733.
Ip, Y. K., Soh, M. M. L., Chen, X. LO., Ong, J. L. Y., Chng, Y. R., Ching B., Wong, W. P., Lam, S. H. and Chew, S. F. (2013). Molecular characterization of branchial aquaporin 1aa and effects of seawater acclimation, emersion or ammonia exposure on its mRNA expression in the gills, gut, kidney and skin of the freshwater climbing perch, Anabas testudineus. PLoS One, Volume: 8 Issue: 4 Article Number: e61163 DOI: 10.1371/journal.pone.0061163
Ip, Y. K., Lee, S. M. L., Wong, W. P., Chew, S. F. (2013). The Chinese soft-shelled turtle, Pelodiscus sinensis, decreases nitrogenous excretion, reduces urea synthesis and suppresses ammonia production during emersion. J. Exp. Biol. 216, 1650-1657.
Wong, S. Z. H., Ching, B., Chng, Y. R., Wong, W. P., Chew, S. F. and Ip, Y. K. (2013). Ascorbic Acid Biosynthesis and Brackish Water Acclimation in the Euryhaline Freshwater White-Rimmed Stingray, Himantura signifier. PLoS ONE 8(6): e66691. doi:10.1371/journal.pone.0066691
Ching, B., Chen, X. L.,Yong, J. H. A., Wilson, J. M., Hiong, K. C., Sim, E. W. L., Wong, W. P., Lam, S. H., Chew, S. F. and Ip, Y. K. (2013). Increases in apoptosis, caspase activity and expression of p53 and bax, and the transition between two types of mitochondrion-rich cells, in the gills of the climbing perch, Anabas testudineus, during a progressive acclimation from freshwater to seawater. Front. Physiol. 4:135. doi: 10.3389/fphys.2013.00135
Amelio, D., Garofalo, F., Wong, W. P., Chew, S. F., Ip, Y. K., Cerra, M. C. and Tota B. (2013). Nitric oxide synthase-dependent "On/Off" switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle. Nitric Oxide 32, 1-12.
Ip, Y. K., Hou, Zhisheng, Chen, X. L., Hiong, K. C. and Chew, S. F. (2013) The relationship between Na+:K+:2Cl- cotransporter and high ammonia tolerance in the brain of the swamp eel, Monopterus albus. PLoS ONE In press
Hiong, K. C., Ip, Y. K., Wong, W. P. and Chew, S. F. (2013) Differential gene expression in the brain of the African lungfish, Protopterus annectens, after six days or six months of aestivation in air. PLoS ONE In press
Chew, S. F., Hiong, K. C., Lam, S. P., and Ip, Y. K. Effects of environmental ammonia and/or seawater exposure on mRNA expression and protein abundance of Na+:K+:2Cl- cotransporter in the gills of the giant mudskipper, Periophthalmodon schlosseri, pre-acclimated to freshwater. PLoS ONE Submitted
Chen, X. L., Wee, N. L. J. E., Hiong, K. C., Ong, J. L. Y., Chng, Y. R., Ching, B., Wong, W. P., Chew, S. F., and Ip, Y. K. High brain ammonia tolerance in the swamp eel, Monopterus albus, exposed to environmental ammonia is attributable to the properties and expression of brain Na+/K+-ATPase α-subunit isoforms. PLoS ONE Submitted