Taurine suppresses the spread of cell death in electrically coupled RPE cells

Purpose To determine whether taurine exerts a protective effect on retinal pigment epithelium (RPE) cells exposed to a cytotoxic agent, cytochrome C (cyC), shown previously to induce apoptosis and produce cell death in electrically coupled neighboring cells. Methods Monolayer cultures of confluent human RPE (ARPE-19) cells, which express gap-junctional proteins, were incubated in culture medium with or without taurine. After scrape loading cyC into the cells, we assayed these cells for caspase 3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine the spread of apoptosis. Results We found that cyC, too large a molecule to traverse gap junctional channels, produced apoptosis in cells injured by the scrape as well as those distant from the site of the scrape, presumably by the intercellular transmission of a toxic agent through the gap junctions that couple these cells. Incubation in taurine, or the gap-junction blocker, octanol, before application of cyC, reduced significantly the fraction of cells undergoing apoptosis. Voltage clamp recordings from electrically coupled Xenopus oocytes transfected with Cx43 showed that junctional communication was unaffected by taurine. Conclusions Our results indicate that taurine can serve to suppress cell death in RPE cells independent of any effect on gap junctions. We have considered various avenues by which taurine can exert its protective effect, but the precise mechanism involved under these experimental conditions has yet to be identified.

[1]  Y. Matsuzaki,et al.  Ursodeoxycholic acid: Mechanism of action and novel clinical applications , 2007, Hepatology research : the official journal of the Japan Society of Hepatology.

[2]  J. Berman,et al.  Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes , 2007, The Journal of Neuroscience.

[3]  G. Salvesen,et al.  The apoptosome: signalling platform of cell death , 2007, Nature Reviews Molecular Cell Biology.

[4]  A. Harris Connexin channel permeability to cytoplasmic molecules. , 2007, Progress in biophysics and molecular biology.

[5]  C. Steer,et al.  Tool from ancient pharmacopoeia prevents vision loss. , 2006, Molecular vision.

[6]  Y. Lazebnik,et al.  Requirement of cytochrome c for apoptosis in human cells , 2006, Cell Death and Differentiation.

[7]  H. Qian,et al.  An electrophysiological study of retinal function in the diabetic female rat. , 2006, Investigative ophthalmology & visual science.

[8]  D. Spray,et al.  Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to ‘bystander’ cell killing , 2006, Cell Death and Differentiation.

[9]  C. Steer,et al.  Tauroursodeoxycholic acid modulates p53‐mediated apoptosis in Alzheimer's disease mutant neuroblastoma cells , 2006, Journal of neurochemistry.

[10]  Aniq B. Darr,et al.  Glucose utilization by the retinal pigment epithelium: evidence for rapid uptake and storage in glycogen, followed by glycogen utilization. , 2006, Experimental eye research.

[11]  R. Eckert Gap-junctional single-channel permeability for fluorescent tracers in mammalian cell cultures. , 2006, Biophysical journal.

[12]  M. Mikov,et al.  Biosynthesis of bile acids in mammalian liver , 2006, European Journal of Drug Metabolism and Pharmacokinetics.

[13]  Yan-min Zhang,et al.  Taurine modulates calcium influx through L-type voltage-gated calcium channels in isolated cochlear outer hair cells in guinea pigs , 2006, Neuroscience Letters.

[14]  S. Oja,et al.  Characteristics of taurine release in slices from adult and developing mouse brain stem , 2006, Amino Acids.

[15]  T. Fujita,et al.  Functional Expression of Taurine Transporter and its Up-Regulation in Developing Neurons from Mouse Cerebral Cortex , 2006, Pharmaceutical Research.

[16]  G. Seghieri,et al.  Taurine supplementation and diabetes mellitus , 2006, Current opinion in clinical nutrition and metabolic care.

[17]  F. Obregón,et al.  Taurine and Zinc Modulate Outgrowth from Goldfish Retinal Explants , 2005, Neurochemical Research.

[18]  H. Ripps,et al.  The spread of apoptosis through gap-junctional channels in BHK cells transfected with Cx32 , 2005, Apoptosis.

[19]  P. Stanton,et al.  Blockade of Gap Junctions In Vivo Provides Neuroprotection After Perinatal Global Ischemia , 2005, Stroke.

[20]  D. Frank,et al.  Single‐cell microinjection of cytochrome c can result in gap junction–mediated apoptotic cell death of bystander cells in head and neck cancer , 2005, Head & neck.

[21]  G. Sosinsky,et al.  Structural organization of gap junction channels. , 2005, Biochimica et biophysica acta.

[22]  P. Vandenabeele,et al.  Gap junctions and the propagation of cell survival and cell death signals , 2005, Apoptosis.

[23]  C. Anuradha,et al.  Effect of taurine on biomarkers of oxidative stress in tissues of fructose-fed insulin-resistant rats. , 2005, Singapore medical journal.

[24]  L. Combettes,et al.  Cholestatic bile acids inhibit gap junction permeability in rat hepatocyte couplets and normal rat cholangiocytes. , 2005, Journal of hepatology.

[25]  Yigong Shi,et al.  Molecular mechanisms of caspase regulation during apoptosis , 2004, Nature Reviews Molecular Cell Biology.

[26]  Y. Fujio,et al.  Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome. , 2004, American journal of physiology. Cell physiology.

[27]  V. Ganapathy,et al.  Death of retinal neurons in streptozotocin-induced diabetic mice. , 2004, Investigative ophthalmology & visual science.

[28]  Joanna S Morris,et al.  Altered permeability and modulatory character of connexin channels during mammary gland development. , 2004, Experimental cell research.

[29]  M. Suleiman,et al.  Myocardial taurine, development and vulnerability to ischemia , 2004, Amino Acids.

[30]  W. E. Orr,et al.  Comparing the use of Affymetrix to spotted oligonucleotide microarrays using two retinal pigment epithelium cell lines. , 2003, Molecular vision.

[31]  C. Anuradha,et al.  Inhibition of lipid peroxidation, protein glycation and elevation of membrane ion pump activity by taurine in RBC exposed to high glucose. , 2003, Clinica chimica acta; international journal of clinical chemistry.

[32]  E. Park,et al.  Taurine: new implications for an old amino acid. , 2003, FEMS microbiology letters.

[33]  B. Himpens,et al.  Intercellular Ca(2+)-transient propagation in normal and high glucose solutions in rat retinal epithelial (RPE-J) cells during mechanical stimulation. , 2003, Cell calcium.

[34]  B. Reese,et al.  Gap Junctions Mediate Bystander Cell Death in Developing Retina , 2003, The Journal of Neuroscience.

[35]  C. Steer,et al.  Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. Bloomfield,et al.  Connexin36 Is Essential for Transmission of Rod-Mediated Visual Signals in the Mammalian Retina , 2002, Neuron.

[37]  A. Trovato-Salinaro,et al.  Virtual cloning, functional expression, and gating analysis of human connexin31.9. , 2002, American journal of physiology. Cell physiology.

[38]  K. Oyanagi,et al.  Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin‐diabetic rats , 2002, Neuropathology : official journal of the Japanese Society of Neuropathology.

[39]  V. Krutovskikh,et al.  Gap junction intercellular communication propagates cell death in cancerous cells , 2002, Oncogene.

[40]  Jang-Yen Wu,et al.  The Role of Taurine in the Central Nervous System and the Modulation of Intracellular Calcium Homeostasis , 2002, Neurochemical Research.

[41]  M. Seeliger,et al.  Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  V. Ganapathy,et al.  Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells. , 2001, American journal of physiology. Cell physiology.

[43]  S. Hansen The role of taurine in diabetes and the development of diabetic complications , 2001, Diabetes/metabolism research and reviews.

[44]  G. Jerums,et al.  Pathogenesis and intervention strategies in diabetic retinopathy. , 2001, Clinical & experimental ophthalmology.

[45]  J. Parys,et al.  Effects of Hyperglycemia and Protein Kinase C on Connexin43 Expression in Cultured Rat Retinal Pigment Epithelial Cells , 2001, The Journal of Membrane Biology.

[46]  T. Gardner,et al.  Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group. , 2000, Investigative ophthalmology & visual science.

[47]  K. Shiraki,et al.  The relationship between gap-junctional intercellular communication and the proliferative activity of retinal pigment epithelial cells. , 2000, Japanese journal of ophthalmology.

[48]  Y. Takei,et al.  Taurine preserves gap junctional intercellular communication in rat hepatocytes under oxidative stress , 2000, Journal of Gastroenterology.

[49]  R. Weiler,et al.  Distribution of Connexin43 immunoreactivity in the retinas of different vertebrates , 1998, The Journal of comparative neurology.

[50]  K. Hardy,et al.  Effects of glutamine and taurine on preimplantation development and cleavage of mouse embryos in vitro. , 1997, Biology of reproduction.

[51]  K. Willecke,et al.  Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[52]  L. Hjelmeland,et al.  ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. , 1996, Experimental eye research.

[53]  H. Trachtman,et al.  Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. , 1995, The American journal of physiology.

[54]  J. Cook,et al.  Gap junctions in the vertebrate retina , 1995, Microscopy research and technique.

[55]  C. Waterfield,et al.  The in vivo and in vitro protective properties of taurine. , 1995, General pharmacology.

[56]  G. Wick,et al.  Methods for the detection of apoptosis. , 1994, International archives of allergy and immunology.

[57]  P. Schnetkamp,et al.  The glucose transporter in the plasma membrane of the outer segments of bovine retinal rods. , 1994, Experimental eye research.

[58]  S. Freeman,et al.  The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified. , 1993, Cancer research.

[59]  Wan Ariffin Bin Abdullah Singapore Med J , 1993 .

[60]  A. Hofmann,et al.  Tissue taurine content, activity of taurine synthesis enzymes and conjugated bile acid composition of taurine-deprived and taurine-supplemented rhesus monkey infants at 6 and 12 mo of age. , 1991, The Journal of nutrition.

[61]  J. Lombardini Taurine: retinal function , 1991, Brain Research Reviews.

[62]  Y. Collan,et al.  Taurine in normal and diseased human skeletal muscle , 1990, Acta neurologica Scandinavica.

[63]  R. Huxtable Taurine in the central nervous system and the mammalian actions of taurine , 1989, Progress in Neurobiology.

[64]  J. D. Del Valle,et al.  Membrane perturbations and mediation of gap junction formation in response to taurine treatment in normal and injured alveolar epithelia. , 1989, Experimental lung research.

[65]  D. Paul,et al.  Cloning and expression of a Xenopus embryonic gap junction protein. , 1989, Science.

[66]  J. Azuma,et al.  Taurine prevention of calcium paradox-related damage in cardiac muscle. Its regulatory action on intracellular cation contents. , 1988, Biochemical pharmacology.

[67]  B. Sakmann,et al.  Patch clamp measurements onXenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels , 1986, Pflügers Archiv.

[68]  R. Gordon,et al.  Taurine protects hamster bronchioles from acute NO2-induced alterations. A histologic, ultrastructural, and freeze-fracture study. , 1986, The American journal of pathology.

[69]  J. Azuma,et al.  Protective effect of taurine against isoprenaline-induced myocardial damage , 1986, Basic Research in Cardiology.

[70]  J. Dimattio,et al.  Facilitated glucose transport across the retinal pigment epithelium of the bullfrog (Rana catesbeiana). , 1986, Experimental eye research.

[71]  C. Kilo,et al.  Absence of degenerative changes in retinal and uveal capillary pericytes in diabetic rats. , 1986, Investigative ophthalmology & visual science.

[72]  F. Matschinsky,et al.  Experimental diabetes mellitus impairs the function of the retinal pigmented epithelium. , 1986, Metabolism: clinical and experimental.

[73]  D C Spray,et al.  Equilibrium properties of a voltage-dependent junctional conductance , 1981, The Journal of general physiology.

[74]  S. Ennis,et al.  The effect of induced diabetes on the electroretinogram components of the pigmented rat. , 1980, Investigative ophthalmology & visual science.

[75]  A. Laties,et al.  A permeability defect of the retinal pigment epithelium. Occurrence in early streptozocin diabetes. , 1980, Archives of ophthalmology.

[76]  D. Vessey The biochemical basis for the conjugation of bile acids with either glycine or taurine. , 1978, The Biochemical journal.

[77]  H. Jasper,et al.  Taurine Treatment of Spontaneous Chronic Epilepsy in a Cat , 1977, Epilepsia.

[78]  A. Hofmann The enterohepatic circulation of bile acids in man. , 1976, Advances in internal medicine.

[79]  O. H. Lowry,et al.  The distribution of taurine in the vertebrate retina , 1976, Journal of neurochemistry.

[80]  N. Lake,et al.  Studies on the uptake of taurine by the isolated neural retina and pigment epithelium of the frog. , 1975, Biochemical Society transactions.

[81]  S. Y. Schmidt,et al.  Retinal degeneration associated with taurine deficiency in the cat. , 1975, Science.

[82]  P. Mandel,et al.  Free amino acids of chicken and rat retina. , 1972, Brain research.

[83]  Yigong Shi,et al.  Apoptosome: a platform for the activation of initiator caspases , 2007, Cell Death and Differentiation.

[84]  R. Salceda,et al.  Glucose Metabolism in Rat Retinal Pigment Epithelium , 2005, Neurochemical Research.

[85]  A. Dosso,et al.  Streptozotocin-induced diabetes--a rat model to study involvement of retinal cell types in the onset of diabetic retinopathy. , 2003, Advances in experimental medicine and biology.

[86]  S H Kaufmann,et al.  Mammalian caspases: structure, activation, substrates, and functions during apoptosis. , 1999, Annual review of biochemistry.

[87]  B. Himpens,et al.  Confocal imaging of Ca2+ signaling in cultured rat retinal pigment epithelial cells during mechanical and pharmacologic stimulation. , 1997, Investigative ophthalmology & visual science.

[88]  G. Seghieri,et al.  Taurine and diabetes. Humans and experimental models. , 1996, Advances in experimental medicine and biology.

[89]  V. Ganapathy,et al.  Properties of taurine transport in a human retinal pigment epithelial cell line. , 1993, Current eye research.

[90]  T. Yoshida,et al.  The protective effect of taurine on the biomembrane against damage produced by the oxygen radical. , 1992, Advances in experimental medicine and biology.

[91]  N. Lake,et al.  Retinal morphology in rats treated with a taurine transport antagonist. , 1987, Experimental eye research.

[92]  H. Wiśniewski,et al.  Dietary taurine is necessary for normal retinal development in monkeys. , 1985, Progress in clinical and biological research.

[93]  K. Kuriyama,et al.  Therapeutic effect of taurine administration on carbon tetrachloride-induced hepatic injury. , 1982, Japanese journal of pharmacology.

[94]  E. Berson,et al.  Retinal degeneration in cats fed casein. I. Taurine deficiency. , 1976, Investigative ophthalmology.

[95]  R. Nayyar,et al.  Histochemical and electron microscopic studies of the retinal pigment epithelium in the normal and diabetic rat. , 1968, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[96]  Hollenberg Mj,et al.  Histochemical and electron microscopic studies of the retinal pigment epithelium in the normal and diabetic rat. , 1968, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.