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      KCI등재 SCOPUS SCIE

      The changes of mitochondrial cytochrome c and GABAergic neuron in neuropathic pain model

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      https://www.riss.kr/link?id=A104327644

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

      Background: Role of cytochrome c (Cyt c) is an apoptogenic agent under certain conditions. The mitochondrial permeability transition pore (MPTP) plays an important role in cell death since it opens, leading to mitochondrial swelling and release of Cyt c, which initiates apoptosis. By inhibiting the opening of MPTP, cyclosporine A (CSA) may contribute to maintaining mitochondrial homeostasis. We investigate the effects of the partial sciatic nerve injury (PSNI)-induced neuropathic pain model on mitochondrial Cyt c release and the effects of CSA on neuroprotection by mitochondrial stabilizing activity in PSNI rats.
      Methods: Rats were assigned to two groups that received different operations (Group P; PSNI operation, Group S; sham operation). The changes of cyt c and GABAergic neuron were evaluated in the spinal cord tissue. After which, PSNI rats randomly received CSA (Group C) or saline (Group S), and the changes of mechanical thresholds with Cyt c and GABAergic neuron were checked.
      Results: PSNI in rats increased the release of cytosolic Cyt c. However, GABAergic cells were not decreased in the spinal cord level on the ipsilateral side to the PSNI. The second experiment reveal a reduction in Cyt c release, using CSA in PSNI model. Rats receiving CSA were afforded the antiallodynia without decrease of GABAergic cell.
      Conclusions: The Cyt c probably contributes to nerve dysfunction after PSNI. PSNI induced neuropathic pain was profoundly linked to mitochondrial stabilization. Thus, the potent neuroprotector, CSA, might produce antiallodynia through its capability to inhibit the opening of MPTP.
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      Background: Role of cytochrome c (Cyt c) is an apoptogenic agent under certain conditions. The mitochondrial permeability transition pore (MPTP) plays an important role in cell death since it opens, leading to mitochondrial swelling and release of Cyt...

      Background: Role of cytochrome c (Cyt c) is an apoptogenic agent under certain conditions. The mitochondrial permeability transition pore (MPTP) plays an important role in cell death since it opens, leading to mitochondrial swelling and release of Cyt c, which initiates apoptosis. By inhibiting the opening of MPTP, cyclosporine A (CSA) may contribute to maintaining mitochondrial homeostasis. We investigate the effects of the partial sciatic nerve injury (PSNI)-induced neuropathic pain model on mitochondrial Cyt c release and the effects of CSA on neuroprotection by mitochondrial stabilizing activity in PSNI rats.
      Methods: Rats were assigned to two groups that received different operations (Group P; PSNI operation, Group S; sham operation). The changes of cyt c and GABAergic neuron were evaluated in the spinal cord tissue. After which, PSNI rats randomly received CSA (Group C) or saline (Group S), and the changes of mechanical thresholds with Cyt c and GABAergic neuron were checked.
      Results: PSNI in rats increased the release of cytosolic Cyt c. However, GABAergic cells were not decreased in the spinal cord level on the ipsilateral side to the PSNI. The second experiment reveal a reduction in Cyt c release, using CSA in PSNI model. Rats receiving CSA were afforded the antiallodynia without decrease of GABAergic cell.
      Conclusions: The Cyt c probably contributes to nerve dysfunction after PSNI. PSNI induced neuropathic pain was profoundly linked to mitochondrial stabilization. Thus, the potent neuroprotector, CSA, might produce antiallodynia through its capability to inhibit the opening of MPTP.

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      참고문헌 (Reference)

      1 Seltzer Z, "novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury" 43 : 205-218, 1990

      2 Brustovetsky N, "Two pathways for tBID-induced cytochrome c release from rat brain mitochondria: BAK- versus BAX-dependence" 84 : 196-207, 2003

      3 Lindsten T, "The proapoptotic activities of Bax and Bak limit the size of the neural stem cell pool" 23 : 11112-11119, 2003

      4 De Giorgi F, "The permeability transition pore signals apoptosis by directing bax translocation and multimerization" 16 : 607-609, 2002

      5 Szabo I, "The giant channel of the inner mitochondrial membrane is inhibited by cyclosporin A" 266 : 3376-3379, 1991

      6 Chaplan SR, "Quantitative assessment of tactile allodynia in the rat paw" 53 : 55-63, 1994

      7 Bartynski WS, "Pretransplantation conditioning influence on the occurrence of cyclosporine or FK-506 neurotoxicity in allogeneic bone marrow transplantation" 25 : 261-269, 2004

      8 Moore KA, "Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord" 22 : 6724-6731, 2002

      9 Snyder SH, "Neural actions of immunophilin ligands" 19 : 21-26, 1998

      10 Cai J, "Mitochondrial control of apoptosis: the role of cytochrome c" 1366 : 139-149, 1998

      1 Seltzer Z, "novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury" 43 : 205-218, 1990

      2 Brustovetsky N, "Two pathways for tBID-induced cytochrome c release from rat brain mitochondria: BAK- versus BAX-dependence" 84 : 196-207, 2003

      3 Lindsten T, "The proapoptotic activities of Bax and Bak limit the size of the neural stem cell pool" 23 : 11112-11119, 2003

      4 De Giorgi F, "The permeability transition pore signals apoptosis by directing bax translocation and multimerization" 16 : 607-609, 2002

      5 Szabo I, "The giant channel of the inner mitochondrial membrane is inhibited by cyclosporin A" 266 : 3376-3379, 1991

      6 Chaplan SR, "Quantitative assessment of tactile allodynia in the rat paw" 53 : 55-63, 1994

      7 Bartynski WS, "Pretransplantation conditioning influence on the occurrence of cyclosporine or FK-506 neurotoxicity in allogeneic bone marrow transplantation" 25 : 261-269, 2004

      8 Moore KA, "Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord" 22 : 6724-6731, 2002

      9 Snyder SH, "Neural actions of immunophilin ligands" 19 : 21-26, 1998

      10 Cai J, "Mitochondrial control of apoptosis: the role of cytochrome c" 1366 : 139-149, 1998

      11 Budd SL, "Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons" 97 : 6161-6166, 2000

      12 Nicholls DG, "Mitochondria and neuronal glutamate excitotoxicity" 1366 : 97-112, 1998

      13 Hokfelt T, "Messenger plasticity in primary sensory neurons following axotomy and its functional implications" 17 : 22-30, 1994

      14 Polgar E, "Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain" 25 : 6658-6666, 2005

      15 Polster BM, "Inhibition of Bax-induced cytochrome c release from neural cell and brain mitochondria by dibucaine and propranolol" 23 : 2735-2743, 2003

      16 Liu X, "Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c" 86 : 147-157, 1996

      17 Castro-Lopes JM, "GABA decreases in the spinal cord dorsal horn after peripheral neurectomy" 620 : 287-291, 1993

      18 Kapur J, "Evidence for a chronic loss of inhibition in the hippocampus after kindling: biochemical studies" 4 : 100-108, 1989

      19 Dixon WJ, "Efficient analysis of experimental observations" 20 : 441-462, 1980

      20 Wigdal SS, "Cytochrome c release precedes mitochondrial membrane potential loss in cerebellar granule neuron apoptosis: lack of mitochondrial swelling" 82 : 1029-1038, 2002

      21 Broekemeier KM, "Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria" 264 : 7826-7830, 1989

      22 Li H, "Cleavage of BID by caspase 8 mediates the mitochondrial damage in the fas pathway of apoptosis" 94 : 491-501, 1998

      23 Zou H, "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3" 90 : 405-413, 1997

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