본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology v.14 no.3, 2010년, pp.127 - 132   SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons

Hahm, Eu-Teum    (Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine   ); Seo, Jung-Woo    (Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine   ); Hur, Jin-Young    (Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine   ); Cho, Young-Wuk    (Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine  );
  • 초록

    Reactive oxygen species (ROS), which include hydrogen peroxide ( $H_2O_2$ ), the superoxide anion ( ${O_2}^-{\cdot}$ ), and the hydroxyl radical ( $OH{\cdot}$ ), are generated as by-products of oxidative metabolism in cells. The cerebral cortex has been found to be particularly vulnerable to production of ROS associated with conditions such as ischemia-reperfusion, Parkinson's disease, and aging. To investigate the effect of ROS on inhibitory GABAergic synaptic transmission, we examined the electrophysiological mechanisms of the modulatory effect of $H_2O_2$ on GABAergic miniature inhibitory postsynaptic current (mIPSCs) in mechanically isolated rat cerebral cortical neurons retaining intact synaptic boutons. The membrane potential was voltage-clamped at -60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM $H_2O_2$ gradually potentiated mIPSCs. This potentiating effect of $H_2O_2$ was blocked by the pretreatment with either 10,000-unit/mL catalase or $300-{\mu}M$ N-acetyl-cysteine. The potentiating effect of $H_2O_2$ was occluded by an adenylate cyclase activator, forskolin, and was blocked by a protein kinase A inhibitor, N -(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide hydrochloride. This study indicates that oxidative stress may potentiate presynaptic GABA release through the mechanism of cAMP-dependent protein kinase A (PKA)-dependent pathways, which may result in the inhibition of the cerebral cortex neuronal activity.


  • 주제어

    Gamma-aminobutyric acid .   Hydrogen peroxide .   Oxidative stress .   Inhibitory postsynaptic potentials.  

  • 참고문헌 (34)

    1. Fridovich I. The biology of oxygen radicals. Science. 1978;201:875-880. 
    2. Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem. 1992;59:1609-1623. 
    3. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA. 1990;87:1620-1624. 
    4. Lewen A, Matz P, Chan PH. Free radical pathways in CNS injury. J Neurotrauma. 2000;17:871-890. 
    5. Ames BN, Shigenaga MK. Oxidants are a major contributor to aging. Ann N Y Acad Sci. 1992;663:85-96. 
    6. Chandra J, Samali A, Orrenius S. Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med. 2000;29:323-333. 
    7. Golino P, Ragni M, Cirillo P, Avvedimento VE, Feliciello A, Esposito N, Scognamiglio A, Trimarco B, Iaccarino G, Condorelli M, Chiariello M, Ambrosio G. Effects of tissue factor induced by oxygen free radicals on coronary flow during reperfusion. Nat Med. 1996;2:35-40. 
    8. Kvaltinova Z, Lukovic L, Stolc S. Effect of incomplete ischemia and reperfusion of the rat brain on the density and affinity of alpha-adrenergic binding sites in the cerebral cortex. Prevention of changes by stobadine and vitamin E. Neuropharmacology. 1993;32:785-791. 
    9. Muakkassah-Kelly SF, Andresen JW, Shih JC, Hochstein P. Decreased [3H]serotonin and [3H]spiperone binding consequent to lipid peroxidation in rat cortical membranes. Biochem Biophys Res Commun. 1982;104:1003-1010. 
    10. Sah R, Schwartz-Bloom RD. Optical imaging reveals elevated intracellular chloride in hippocampal pyramidal neurons after oxidative stress. J Neurosci. 1999;19:9209-9217. 
    11. Schwartz RD. The GABAA receptor-gated ion channel: bio-chemical and pharmacological studies of structure and function. Biochem Pharmacol. 1988;37:3369-3375. 
    12. van der Want JJ, Nunes Cardozo JJ, van der TC. GABAergic neurons and circuits in the pretectal nuclei and the accessory optic system of mammals. Prog Brain Res. 1992;90:283-305. 
    13. Finkel T. Oxygen radicals and signaling. Curr Opin Cell Biol. 1998;10:248-253. 
    14. Nakamura K, Hori T, Sato N, Sugie K, Kawakami T, Yodoi J. Redox regulation of a src family protein tyrosine kinase p56lck in T cells. Oncogene. 1993;8:3133-3139. 
    15. Klann E, Roberson ED, Knapp LT, Sweatt JD. A role for superoxide in protein kinase C activation and induction of long-term potentiation. J Biol Chem. 1998;273:4516-4522. 
    16. Whisler RL, Goyette MA, Grants IS, Newhouse YG. Sublethal levels of oxidant stress stimulate multiple serine/threonine kinases and suppress protein phosphatases in Jurkat T cells. Arch Biochem Biophys. 1995;319:23-35. 
    17. Rego AC, Santos MS, Oliveira CR. Oxidative stress, hypoxia, and ischemia-like conditions increase the release of endogenous amino acids by distinct mechanisms in cultured retinal cells. J Neurochem. 1996;66:2506-2516. 
    18. Takahashi A, Mikami M, Yang J. Hydrogen peroxide increases GABAergic mIPSC through presynaptic release of calcium from IP3 receptor-sensitive stores in spinal cord substantia gelatinosa neurons. Eur J Neurosci. 2007;25:705-716. 
    19. Akaike N, Moorhouse AJ. Techniques: applications of the nerve-bouton preparation in neuropharmacology. Trends Pharmacol Sci. 2003;24:44-47. 
    20. Hahm ET, Lee JJ, Min BI, Cho YW. Opioid inhibition of GABAergic neurotransmission in mechanically isolated rat periaqueductal gray neurons. Neurosci Res. 2004;50:343-354. 
    21. Min BI, Kim CJ, Rhee JS, Akaike N. Modulation of glycineinduced chloride current in acutely dissociated rat periaqueductal gray neurons by $\mu$-opioid agonist DAGO. Brain Res. 1996;734:72-78. 
    22. Lin HH, Chen CH, Hsieh WK, Chiu TH, Lai CC. Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons in vivo and in vitro. Neuroscience. 2003;121:641-647. 
    23. Volterra A, Trotti D, Racagni G. Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms. Mol Pharmacol. 1994;46:986-992. 
    24. Mailly F, Marin P, Israel M, Glowinski J, Premont J. Increase in external glutamate and NMDA receptor activation contribute to $H_{2}O_{2}$-induced neuronal apoptosis. J Neurochem. 1999;73:1181-1188. 
    25. Lee MK, Yeo H, Kim J, Markelonis GJ, Oh TH, Kim YC. Cynandione A from Cynanchum wilfordii protects cultured cortical neurons from toxicity induced by $H_{2}O_{2}$, L-glutamate, and kainate. J Neurosci Res. 2000;59:259-264. 
    26. Lee JJ, Hahm ET, Lee CH, Cho YW. Serotonergic modulation of GABAergic and glutamatergic synaptic transmission in mechanically isolated rat medial preoptic area neurons. Neuropsychopharmacology. 2008;33:340-352. 
    27. Jeong HJ, Jang IS, Nabekura J, Akaike N. Adenosine A1 receptor-mediated presynaptic inhibition of GABAergic transmission in immature rat hippocampal CA1 neurons. J Neurophysiol. 2003;89:1214-1222. 
    28. Schwartz-Bloom RD, Sah R. gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem. 2001;77:353-371. 
    29. Dreher D, Junod AF. Differential effects of superoxide, hydrogen peroxide, and hydroxyl radical on intracellular calcium in human endothelial cells. J Cell Physiol. 1995;162:147-153. 
    30. Joseph JA, Erat S, Denisova N, Villalobos-Molina R. Receptorand age-selective effects of dopamine oxidation on receptor-G protein interactions in the striatum. Free Radic Biol Med. 1998;24:827-834. 
    31. Denu JM, Tanner KG. Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry. 1998;37:5633-5642. 
    32. Saransaari P, Oja SS. Release of endogenous glutamate, aspartate, GABA, and taurine from hippocampal slices from adult and developing mice under cell-damaging conditions. Neurochem Res. 1998;23:563-570. 
    33. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981;391:85-100. 
    34. Yum DS, Cho JH, Choi IS, Nakamura M, Lee JJ, Lee MG, Choi BJ, Choi JK, Jang IS. Adenosine A1 receptors inhibit GABA-ergic transmission in rat tuberomammillary nucleus neurons. J Neurochem. 2008;106:361-371. 

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기