AAR  Vol.4 No.2 , March 2015
Therapeutic Potential of 17β Estradiol with Tachykinin Neuropeptide NKB and Aβ(25 - 35) on Na+ - K+ ATPase Activity in Aging Female Rat Brain

The Na+ - K+ ATPase is an enzyme responsible for the active transport of Na+ and K+ in most eukaryotic cells. The aim of the present study was to determine the effect of Tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 - 35) on 17β estradiol (E2) treated aging female rat brain synaptosomes of different age groups, by assaying Na+ - K+ ATPase enzyme activity. An in vitro incubation of isolated synaptosomes with Aβ (25 - 35) showed toxic effects while NKB showed stimulating effect on the Na+ - K+ ATPase activity, and the combined NKB + Aβ (25 - 35) incubations showed a partial effect as compared to the Aβ (25 - 35) alone. To understand whether E2 affects the expression of Na+ - K+ ATPase molecules, we examined the expression of Na+ - K+ ATPase subunit α1 and β2 in E2 treated aging female rat brain synaptosomes. The enzyme was quantified by SDS PAGE in control and E2 treated rat brain. We observed that the expression of α1 and β2 Na+ - K+ ATPase molecules increased and reversed to a normal level in E2 treated synaptosomes. These results confirmed that E2 increased turnover of Na+ - K+ ATPase molecules in aging rat brain. The present findings also suggest a possible role of NKB with E2 in the age related changes in the brain.

Cite this paper
Jha, R. , Mishra, P. , Kumar, R. , Mahdi, A. , Pandey, S. , Baquer, N. and Cowsik, S. (2015) Therapeutic Potential of 17β Estradiol with Tachykinin Neuropeptide NKB and Aβ(25 - 35) on Na+ - K+ ATPase Activity in Aging Female Rat Brain. Advances in Aging Research, 4, 19-27. doi: 10.4236/aar.2015.42003.
[1]   Poon, H.F.,Vaishnav, R.A., Getchell, T.V., Getchell, M.L. and Butterfield, D.A. (2006) Quantitative Proteomics Analysis of Differential Protein Expression and Oxidative Modification of Specific Proteins in the Brains of Old Mice. Neurobiology of Aging,27, 1010-1019.

[2]   Leutner, S., Eckert, A. and Muller, W.E. (2001) ROS Generation,Lipid Peroxidation and Antioxidant Enzyme Activities in the Aging Brain. Journal of Neural Transmission,108, 955-967.

[3]   Biessels, G.J., van der Heide, L.P., Kamal, A.,Bleys, R.L. and Gispen, W.H. (2002) Ageing and Diabetes: Implications for Brain Function. European Journal of Pharmacology,441, 1-14.

[4]   Calabrese, V., Cornelius, C., Mancuso, C., Pennisi, G., Calafato, S., Bellia, F., Bates, T.E., Giuffrida Stella, A.M., Schapira, T., DinkovaKostova, A.T. and Rizzarelli, E. (2008) Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotectionin Aging, Neurodegenerative Disorders and Longevity. Neurochemical Research, 33, 2444-2471.

[5]   Barker, R. (1991) Substance P and Neurodegenerative Disorders. A Speculative Review. Neuropeptides,20, 73-78. http://dx.doi.org/10.1016/0143-4179(91)90054-M

[6]   Lingrel, J.B.,Orlowski, J., Shull, M.M. and Price, E.M. (1990) Molecular Genetics of Na+- K+ ATPase. Progress in Nucleic Acid Research and Molecular Biology,38, 37-89.http://dx.doi.org/10.1016/S0079-6603(08)60708-4

[7]   Shepherd, G.M. (1994) Neurobiology.3rd Edition, Oxford University Press, Oxford.

[8]   Bertorello, A.M.,Aperia, A.,Walaas, S.I.,Nairn, A.C. and Greengard, P. (1991) Phosphorylation of the Catalytic Subunit of Na+- K+ ATPase Inhibits the Activity of the Enzyme. Proceedings of the National Academy of Sciences,88, 11359-11362.http://dx.doi.org/10.1073/pnas.88.24.11359

[9]   Antonicek, H.,Persohn, E. and Schachner, M. (1987) Biochemical and Functional Characterization of a Novel Neuron-Glia Adhesion Molecule That Is Involved in Neuronal Migration. The Journal of Cell Biology, 104, 1587-1595. http://dx.doi.org/10.1083/jcb.104.6.1587

[10]   Harada, K., Lin, H., Endo, Y.,Fujishiro, N., Sakamoto, Y. and Inoue, M. (2006) Subunit Composition and Role of Na+, K+-ATPase in Ventricular Myocytes. The Journal of Physiological Sciences, 56, 113-121. http://dx.doi.org/10.2170/physiolsci.RP001905

[11]   Beal, M.F. (1995) Aging, Energy and Oxidative Stress in Neurodegenerative Diseases. Annals of Neurology, 38, 357- 366.http://dx.doi.org/10.1002/ana.410380304

[12]   Fleuranceau-Morel, P., Barrier, L., Fauconneau, B., Piriou, A. and Huguet, F (1999) Origin of 4-Hydroxynonenal Incubation Induced Inhibition of Dopamine Transporter and Na+/K+ Adenosine Triphosphate in Rat Striatal Synaptosomes. Neuroscience Letters, 277, 91-94.

[13]   Lehotsky, J., Kaplan, P., Racay, P., Matejovicova, M., Drgova, A. and Mezesova, V. (1999) Membrane Ion Transport Systems during Oxidative Stress in Rodent Brain: Protective Effect of Stobadine and Other Antioxidants. Life Sciences, 65, 1951-1958. http://dx.doi.org/10.1016/S0024-3205(99)00454-3

[14]   Tanaka, Y. and Ando, S. (1990) Synaptic Aging as Revealed by Changes in Membrane Potential and Decreased Activity of Na+, K+-ATPase. Brain Research, 506, 46-52.

[15]   Viani, P., Cervato, G., Fiorilli, A. and Cestaro, B. (1991) Age Related Differences in SynaptosomalPeroxidative Damage and Membrane Properties. Journal of Neurochemistry, 56, 253-258. http://dx.doi.org/10.1111/j.1471-4159.1991.tb02589.x

[16]   Jha, R., Mahdi, A.A., Pandey, S., Baquer, N.Z. and Cowsik, S.M. (2013) Effects of Tachykinin Neuropeptide NKB and Aβ(25-35) on Antioxidant Enzymes Status in 17βEstradiol Treated Aging Female Rats. Advances in Aging Research, 2, 137-143. http://dx.doi.org/10.4236/aar.2013.24020

[17]   Jha, R., Mahdi, A.A., Pandey, S., Baquer, N.Z. and Cowsik, S.M. (2013) Neuroprotective role of 17β Estradiol with Tachykinin Neuropeptide NKB and Aβ (25-35) in Aging Female Rat Brain.Advances in Aging Research,2, 130-136. http://dx.doi.org/10.4236/aar.2013.24019

[18]   Jha, R., Mahdi, A.A., Pandey, S., Baquer, N.Z. and Cowsik, S.M. (2014) Age-Related Changes in Membrane Fluidity and Fluorescence Intensity by Tachykinin Neuropeptide NKB and Aβ (25-35) with 17β Estradiol in Female Rat Brain. American Journal of Experimental and Clinical Research, 1, 25-30.

[19]   Henderson, V.W. (2010) Action of Estrogens in the Aging Brain: Dementia and Cognitive Aging. BiochimicaetBiophysicaActa(BBA)—General Subjects,1800, 1077-1083.

[20]   Dobson, C.M. (2003) Protein Folding and Misfolding. Nature, 426, 884-890.

[21]   Garcia-Segura, L.M., Azcoitia, I. and DonCarlos, L.L. (2001) Neuroprotection by Estradiol. Progress in Neurobiology, 63, 29-60. http://dx.doi.org/10.1016/S0301-0082(00)00025-3

[22]   Simpkins, J.W., Singh, M. and Bishop, J. (1994) The Potential Role for Estrogen Replacement Therapy in the Treatment of Cognitive Decline and Neurodegeneration Associated with Alzheimer’s Disease. Neurobiology of Aging, 2, 195-197. http://dx.doi.org/10.1016/0197-4580(94)90205-4

[23]   Behl, C. (1999) Alzheimer’s Disease and Oxidative Stress: Implications for Novel Therapeutic Approaches. Progress in Neurobiology, 57, 301-323.

[24]   Patacchini, R., Lecci, A., Holzer, P. and Maggi, C.A. (2004) Newly Discovered Tachykinins Raise New Questions about Their Peripheral Roles and the Tachykinin Nomenclature. Trends in Pharmacological Sciences, 25, 1-3. http://dx.doi.org/10.1016/j.tips.2003.11.005

[25]   Almeida, T.A., Rojo, J., Nieto, P.M., Pinto, F.M., Hernandez, M., Martin, J.D. and Candenas, M.L. (2004) Tachykinins and Tachykinin Receptors: Structure and Activity Relationships. Current Medicinal Chemistry, 11, 2045-2081. http://dx.doi.org/10.2174/0929867043364748

[26]   Turska, E., Lachowicz, L. and Wasiak, T. (1985) Effect of Analogues of Substance P Fragments on the MAO Activity in Rat Brain. General Pharmacology: The Vascular System, 16, 293-235.

[27]   Mantha, A.K., Moorthy, K., Cowsik, S.M. and Baquer, N.Z. (2006) Neuroprotective Role of Neurokinin B (NKB) on Amyloid β (25-35) Induced Toxicity in Aging Rat Brain Synaptosomes: Involvement in Oxidative Stress and Excitotoxicity. Biogerentology, 7, 1-17.

[28]   Mantha, A.K., Moorthy, K., Cowsik, S.M. and Baquer, N.Z. (2006) Membrane Associated Functions of Neurokinin B (NKB) on Aβ(25-35) Induced Toxicity in Aging Rat Brain Synaptosomes. Biogerentology, 7, 19-33. http://dx.doi.org/10.1007/s10522-005-6044-z

[29]   Yankner, B.A., Duffy, L.K. and Kirschner, D.A. (1990) Neurotrophic and Neurotoxic Effects of Amyloid Beta Protein: Reversal by Tachykinin Neuropeptides.Science, 250, 279-282.

[30]   Kowall, N.W., Beal, M.F., Buscigliot, J., Duffyt, L.K. and Yankner, N.W. (1991) An in Vivo Model for the Neurodegenerative Effects of β Amyloid and Protection by Substance P. Neurobiology, 88, 7247-7251.

[31]   Maggio, J.E. (1988) Tachykinins. Annual Review of Neuroscience, 11, 13-28.

[32]   Pennefather, J.N., Lecci, A., Candenas, M.L., Patak, E., Pinto, F.M. and Maggi, C.A (2004) Tachykinins and Tachykinin Receptors: A Growing Family.Life Sciences, 74, 1445-1463.

[33]   Moorthy, K., Yadav, U.C.S., Siddiqui, M.R., Basir, S.F., Sharma, D. and Baquer, N.Z. (2004) Effect of Estradiol and Progesterone Treatment on Carbohydrate Metabolizing Enzymes in Tissues of Aging Female Rats. Biogerontology, 5, 249-259. http://dx.doi.org/10.1023/B:BGEN.0000038026.89337.02

[34]   Mayanil, C.S., Kazmi, S.M. and Baquer, N.Z. (1982) Na+, K+-ATPase and Mg2+-ATPase Activities in Different Regions of Rat Brain during Alloxan Diabetes. Journal of Neurochemistry, 39, 903-908.

[35]   Bradford, M.M. (1976) A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochemistry, 72, 248-254.

[36]   Towbin, H. and Gordon, J. (1984) Immunoblotting and Dot Immunobinding Current Status and Outlook. Journal of Immunological Methods, 72, 313-340.

[37]   Kaur, J., Sharma, D. and Singh, R. (1998) Regional Effects of Aging on Na+, K+-ATPase Activity in Rat Brain and Correlation with Multiple Unit Action Potentials and Lipid Peroxidation. Indian Journal of Biochemistry and Biophysics, 35, 364-371.

[38]   Chakraborty, H., Sen, P., Sur, A., Chatterjee, U. and Chakrabarti, S. (2003) Age Related Oxidative Inactivation of Na+-K+-ATPase in Rat Brain Crude Synaptosomes. Experimental Gerontology, 38, 705-710. http://dx.doi.org/10.1016/S0531-5565(03)00066-4

[39]   Tanaka, Y. and Ando, S. (1992) Age Related Changes in [3H] Ouabain Binding to Synaptic Plasma Membranes Isolated from Mouse Brains. Journal of Biochemistry, 112, 117-121.

[40]   Gorini, A., Canosi, U., Devecch, I.E., Geroldi, D. and Villa, R.F. (2002) ATPases Enzyme Activities during Aging in Different Types of Somatic and Synaptic Plasma Membranes from Rat Frontal Cerebral Cortex. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 26, 81-90. http://dx.doi.org/10.1016/S0278-5846(01)00233-0

[41]   Urayamatr, O., Shutt, H. and Sweadner, J.K. (1989) Identification of Three Isozyme Protein of the Catalytic Subunit of the Na,K-ATPase in Rat Brain. The Journal of Biological Chemistry, 264, 8271-8280.

[42]   McGrail, K.M., Phillips, J.M. and Sweadner, K.J. (1991) LmmunofluorescentLocalization of Three Na, K-ATPaseIsozymes in the Rat Central Nervous System: Both Neurons and Glia Can Express More than One Na, K-ATPase. The Journal of Neuroscience, 11, 381-391.