Sıçan (Rattus norvegicus)’da Uzun Süreli Demir Toksisitesi ile Uyarılan Sintaksin4 ve Sinapsin3 mRNA Seviyeleri

Demir beyin dokusu için gerekli olmasına rağmen aşırı birikimi nörodejeneratif rahatsızlıkların yanındabirçok metabolik bozukluklara neden olmaktadır. Sintaksin4 ve sinapsin3 nörotransmitter salınımında rol oynayansinaptik veziküller ile ilişkili proteinlerdir. Biz bu çalışmada ferrik demirin (Fe3+) 0.87 ppm, 3 ppm, 30 ppm ve 300ppm subletal dozlarına maruz kalmış sıçanların (Rattus norvegicus) korteks ve hipokampus dokularındaki sinirhücre sinyal iletiminde fonksiyonu olan Sintaksin4 ve Synapsin3 proteinlerini kodlayan genlerin mRNA seviyeleriüzerine etkilerini araştırdık. Sintaksin4 geninin mRNA seviyesi korteks dokusunda değişmez iken hipokampusdokusunda 30 ppm ve 300 ppm maruziyeti ile mRNA seviyesi azalmıştır. Hem korteks hem de hipokampusdokularında sinapsin3 geni mRNA seviyesi artmıştır.

Anahtar Kelimeler:

Demir birikimi, mRNA ifadesi, sintaksin4, sinapsin3

Syntaxin4 and Synapsin3 mRNA Levels Induced by Long-Term Iron Toxicity in Rat (Rattus norvegicus)

Although iron is necessary for brain tissue, its overload causes many metabolic disorders as wellas neurodegenerative disorders. Syntaxin4 and synapsin3 are proteins associated with synaptic vesicles that playa role in neurotransmitter release. In this study we investigated the effects of sublethal doses of ferric iron at 0.87ppm, 3 ppm, 30 ppm and 300 ppm on mRNA levels of genes coding syntaxin4 and synapsin3 proteins that functionin nerve cell signal transmission in cortex and hippocampus tissues of rats (Rattus norvegicus). While mRNA levelof the syntaxin4 gene was unchanged in the cortex, mRNA level of syntaxin4 decreased with 30 ppm and 300 ppmexposure in the hippocampus. mRNA level of synapsin3 gene in both cortex and hippocampus tissues increased inall treatment groups compared to control group.

Keywords:

Iron overload, mRNA expression, syntaxin4, synapsin3,

PDF

___

Bijlard M, Klunder B, de Jonge JC, Nomden A, Tyagi S, de Vries H, Hoekstra D, Baron W, 2015. Transcriptional expression of myelin basic protein in oligodendrocytes depends on functional syntaxin 4: a potential correlation with autocrine signaling. Molecular and Cellular Biology, 35(4): 675-687.
Bishop GM, Robinson SR, Liu Q, Perry G, Atwood CS, Smith MA, 2002. Iron: a pathological mediator of Alzheimer disease?. Developmental Neuroscience, 24(2-3): 184-187.
Bradl H, (2005). Heavy metals in the environment: origin, interaction and remediation. First Edition. London, United Kingdom, 282 p.
Chen Q, Che R, Wang X, O’Neill FA, Walsh D, Tang W,Shi Y, He L, Kendler KS, Chen X, 2009. Association and expression study of synapsin III and schizophrenia. Neuroscience Letters, 465(3): 248-251.
Chen YA, Scheller RH, 2001. SNARE-mediated membrane fusion. Nature Reviews Molecular Cell Biology, 2(2): 98-106.
Chi P, Greengard P, Ryan TA, 2001. Synapsin dispersion and reclustering during synaptic activity. Nature neuroscience, 4(12): 1187-1193.
Cooper GP, Suszkiw JB, Manalis RS, 1983. Heavy metals: effects on synaptic transmission. Neurotoxicology, 5(3): 247-266.
Dexter DT, Carayon A, Javoy-Agid F, Agid Y, Wells FR, Daniel SE, Lees AJ, Jenner P, Marsden CD, 1991. Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain, 114(4): 1953-1975.
Feng J, Chi P, Blanpied TA, Xu Y, Magarinos AM, Ferreira A, Takahashi RH, Kao HT, McEven BS, Ryan TA, Augustine GJ, 2002. Regulation of neurotransmitter release by synapsin III. Journal of Neuroscience, 22(11): 4372-4380.
Harris KP, Zhang YV, Piccioli ZD, Perrimon N, Littleton JT, 2016. The postsynaptic t-SNARE Syntaxin 4 controls traffic of Neuroligin 1 and Synaptotagmin 4 to regulate retrograde signaling. Elife, 5: e13881.
Hentze MW, Muckenthaler MU, Andrews NC (2004) Balancing acts; molecular control of mammalian iron metabolism. Cell, 117:285–297
Jahn R, Scheller, RH, 2006. SNAREs-engines for membrane fusion. Nature Reviews Molecular Cell Biology, 7(9): 631-643.
Johnson EM, Ueda T, Maeno H, Greengard P, 1972. Adenosine 3', 5-Monophosphatedependent Phosphorylation of a Specific Protein in Synaptic Membrane Fractions from Rat Cerebrum. Journal of Biological Chemistry, 247(17): 5650-5652.
Kao HT., Porton B, Czernik AJ, Feng J, Yiu G, Häring M, Benfenati F, Greengard P, 1998. A third member of the synapsin gene family. Proceedings of the National Academy of Sciences, 95(8): 4667-4672.
Kaur D, Andersen J, 2004. Does cellular iron dysregulation play a causative role in Parkinson’s disease?. Ageing Research Reviews, 3(3): 327-343.
Kile BM, Guillot TS, Venton BJ, Wetsel WC, Augustine GJ, Wightman RM, 2010. Synapsins differentially control dopamine and serotonin release. Journal of neuroscience, 30(29): 9762-9770.
Martens S, McMahon HT, 2008. Mechanisms of membrane fusion: disparate players and common principles. Nature Reviews Molecular Cell Biology, 9(7): 543-556.
Meyron-Holtz EG, Ghosh MC, Rouault TA, 2004. Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306: 2087–2090
Moos T, Morgan EH, 2004. The metabolism of neuronal iron and its pathogenic role in neurological disease: review. Annals of the New York Academy of Sciences, 1012(1): 14-26.
Pfaffl MW, 2001. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Research, 29(9): e45-e45.
Pieribone VA, Shupliakov O, Brodin L, Hilfiker-Rothenfluh S, 1995. Distinct pools of synaptic vesicles in neurotransmitter release. Nature, 375(6531): 493-497.
Ponka P, 2004. Hereditary causes of disturbed iron homeostasis in the central nervous system. Annals of the New York Academy of Sciences, 1012(1): 267-281.
Porton B, Rodriguiz RM, Phillips LE, Gilbert J, Feng J, Greengard P, Kao HT, Wetsel WC, 2010. Mice lacking synapsin III show abnormalities in explicit memory and conditioned fear. Genes, Brain and Behavior, 9(3): 257-268.
Porton B, Wetsel WC, Kao HT, 2011. Synapsin III: role in neuronal plasticity and disease. In Seminars in Cell & Developmental Biology 22(4): 416-424.
Stöber G, Meyer J, Nanda I, Wienker TF, Saar K, Knapp M, Jatske S, Schmid M,Lesch KP, Beckmann H, 2000. Linkage and family‐based association study of schizophrenia and the synapsin III locus that maps to chromosome 22q13. American Journal of Medical Genetics, 96(3): 392-397.
Tao-Cheng JH, Pham A, Yang Y, Winters CA, Gallant PE, Reese TS, 2015. Syntaxin 4 is concentrated on plasma membrane of astrocytes. Neuroscience, 286: 264-271.