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Plasminogen activation in multiple sclerosis and other central nervous system diseases
TIIE EFFECT OF OXYGEN FREE RADICALS ON MYOCARDIAL NUCLEAR CALCIUM TRANSPORT IN RAT
THE INTESTINAL CONTRACTILITY AND ANTI-NGF S. Yavuzer, E. Koc, A. B. Ocakcioglu, A. Yaman,
P. Y. Wang, X. H. Yao, X. F. Meng, Y. Z. Pang, Su J. Tang, C. S. Tang Institute of Cardiovascular Research, Beijing Medical University, Beijing 100083, P R. China
A. Elhan University of Ankara, Faculty of Medicine, Departments of Physiology and Biostatistics,Ankara, Tiirkiye In the presented study, it was aimed to investigate the effects of absence of nerve growth factor (NGF) activity on intestinal contractility. Rats were intraperitoneally administered anti-NGF as 1 rig/g (Groupl), 10 rig/g (Group 2), 40 rig/g (Group3) and saline(contro1 group). Seven days after the injections, rats were sacrificed and ileum segments were isolated. Responses of isolated ileums to acetylcholine were evaluated by using standard tyrode, tyrode containing 2xCa2+ and containing no Ca”. l-The control group’s contraction amplitude was found to be higher (pcO.05) in tyrode with 2xCaZ+ and significantly lower (~‘0.05) in tyrode without Ca2+ with respect to standard tyrode. 2-In anti-NGF administered groups contraction amplitudes were higher in tyrode with 2xCa2+ (PC 0.05) and lower in 1 and 10 rig/g administered groups in tyrode without Ca2+ with respect to standard tyrode solution. 3-a) In standard tyrode and tyrode with 2xCa2+ the contraction amplitudes of groups 1 and 3 were significantly lower when compared with the control group (pcO.05). b) However, in tyrode without Ca*+ there were no significant differences between the control and the experimental groups. According to the results achieved, application of anti-NGF seemed to reduce the contractile response most probably by decreasing the Ca2+ passage from extracellular to the intracellular medium.
Objective: To investigate
the effects of oxygen free on myocardial calcium transport system. Methods: Rabbit myocardial nuclei were isolated and purified with sucrose density centrifugation, the activity of Ca-ATPase was measured enzymologically and calcium uptake was assayed with 45Ca2+. Results: Hz02 and hydrosuperoxide (.OH) at low concentration stimulated nuclear Ca-ATPase activity by 31.6% (pcO.05) and 45.8% @
023 THE ANTIBODIES AS TRIGGERS OF THE TENSION OSCILLATIONS IN RAT PAPILLARY MUSCLES
PLASMINOGEN ACTIVATION IN MULTIPLE SCLEROSIS AND OTHER CENTRAL NERVOUS SYSTEM DISEASES
R. I. Yanchiy, Yu. P. Bidzilya, 0. R. Yanchiy, Ya. M. Gotsulyak. immunology, Bogomoletz Institute of Department Physiology Nat. Acad. Sci., Kyiv, Ukraine. E-mail: imm@erv. biph. kiev.ua
F. 0. T. Akenami’, M. Koskiniemi’, V. Siren’, S. Mustjoki’, M. Flrkkila2, and A. Vaheri’ ‘Haartman Institute, and ‘Department of Neurology FIN-00014 University of Helsinki, FINLAND tPA gene activation has been observed in the developing brain and has been associated with motor learning. Moreover, unlike normal mice, tPA-knockout mice are resistant to neuronal destruction after injections of excitotoxins. MS is a chronic demyelinating disease of the CNS of largely unknown etiology. Using immunocapture assay and zymography, we discovered that patients with MS and to a lesser extent leukemia and encephalitis had very high tPA activity in the CSF. The difference between MS and reference subjects was >lO fold. The PAI-1 levels in the same patients were the reverse of their corresponding tPA activities: being higher in leukaemia and encephalitis, than MS. Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples quantitated. In a preliminary study, dexamethasone treatment reduced the CSF tPA activity in MS patients. Conclusively, plasminogen activation seems implicated in neurological diseases, especially MS. While normal tPA levels may be of physiological benefit to the brain, it seems that exaggerated levels are damaging to neuronal cells. The assessment of tPA activity and PAI- may be useful for understanding the pathogenesis/ prognosis of MS and similar neurological diseases. We now use in situ hybridization and immunohistochemistry to localize tPA gene expression in tissue sections and are setting up mouse models to study the role of tPA in demyelinating disorders.
The action of antibodies, specific to membrane of sarcoplasmic reticulum, on the tonic tension (TT) development and sensitivity of the contractile proteins to Ca2’ of skied rat papillary muscles is investigated. It was shown that the antibodies in dose O,l-1,0 mg protein/ml evoke the additional increase in tonic tension on 3-5 min of the antibodies action. The increase run up to 40 % of initial values. The previous blockade of Ca2’ release from intracellular stores by ruthenium red and also its initiation by caffeine (ryanodme) removed the development of the tension oscillations. The increase of the antibody-dependent IT is not bound with growth of the sensitivity of contractile proteins to Ca ions, since the relations pCa2+--relative tension are not changed at various concentrations of Ca2+ and antibodies. These data demonstrate that one of reasons responsible for Ca2+ overload of cardiac myocytes during immunogenic damage is the antibody-dependent Ca2’ release from the sarcoplasmic reticulum pools.
138
THE INTESTINAL CONTRACTILITY AND ANTI-NGF S. Yavuzer, E. Koc, A. B. Ocakcioglu, A. Yaman,
P. Y. Wang, X. H. Yao, X. F. Meng, Y. Z. Pang, Su J. Tang, C. S. Tang Institute of Cardiovascular Research, Beijing Medical University, Beijing 100083, P R. China
A. Elhan University of Ankara, Faculty of Medicine, Departments of Physiology and Biostatistics,Ankara, Tiirkiye In the presented study, it was aimed to investigate the effects of absence of nerve growth factor (NGF) activity on intestinal contractility. Rats were intraperitoneally administered anti-NGF as 1 rig/g (Groupl), 10 rig/g (Group 2), 40 rig/g (Group3) and saline(contro1 group). Seven days after the injections, rats were sacrificed and ileum segments were isolated. Responses of isolated ileums to acetylcholine were evaluated by using standard tyrode, tyrode containing 2xCa2+ and containing no Ca”. l-The control group’s contraction amplitude was found to be higher (pcO.05) in tyrode with 2xCaZ+ and significantly lower (~‘0.05) in tyrode without Ca2+ with respect to standard tyrode. 2-In anti-NGF administered groups contraction amplitudes were higher in tyrode with 2xCa2+ (PC 0.05) and lower in 1 and 10 rig/g administered groups in tyrode without Ca2+ with respect to standard tyrode solution. 3-a) In standard tyrode and tyrode with 2xCa2+ the contraction amplitudes of groups 1 and 3 were significantly lower when compared with the control group (pcO.05). b) However, in tyrode without Ca*+ there were no significant differences between the control and the experimental groups. According to the results achieved, application of anti-NGF seemed to reduce the contractile response most probably by decreasing the Ca2+ passage from extracellular to the intracellular medium.
Objective: To investigate
the effects of oxygen free on myocardial calcium transport system. Methods: Rabbit myocardial nuclei were isolated and purified with sucrose density centrifugation, the activity of Ca-ATPase was measured enzymologically and calcium uptake was assayed with 45Ca2+. Results: Hz02 and hydrosuperoxide (.OH) at low concentration stimulated nuclear Ca-ATPase activity by 31.6% (pcO.05) and 45.8% @
023 THE ANTIBODIES AS TRIGGERS OF THE TENSION OSCILLATIONS IN RAT PAPILLARY MUSCLES
PLASMINOGEN ACTIVATION IN MULTIPLE SCLEROSIS AND OTHER CENTRAL NERVOUS SYSTEM DISEASES
R. I. Yanchiy, Yu. P. Bidzilya, 0. R. Yanchiy, Ya. M. Gotsulyak. immunology, Bogomoletz Institute of Department Physiology Nat. Acad. Sci., Kyiv, Ukraine. E-mail: imm@erv. biph. kiev.ua
F. 0. T. Akenami’, M. Koskiniemi’, V. Siren’, S. Mustjoki’, M. Flrkkila2, and A. Vaheri’ ‘Haartman Institute, and ‘Department of Neurology FIN-00014 University of Helsinki, FINLAND tPA gene activation has been observed in the developing brain and has been associated with motor learning. Moreover, unlike normal mice, tPA-knockout mice are resistant to neuronal destruction after injections of excitotoxins. MS is a chronic demyelinating disease of the CNS of largely unknown etiology. Using immunocapture assay and zymography, we discovered that patients with MS and to a lesser extent leukemia and encephalitis had very high tPA activity in the CSF. The difference between MS and reference subjects was >lO fold. The PAI-1 levels in the same patients were the reverse of their corresponding tPA activities: being higher in leukaemia and encephalitis, than MS. Samples were qualitatively screened for both tPA and uPA activity by zymography and positive samples quantitated. In a preliminary study, dexamethasone treatment reduced the CSF tPA activity in MS patients. Conclusively, plasminogen activation seems implicated in neurological diseases, especially MS. While normal tPA levels may be of physiological benefit to the brain, it seems that exaggerated levels are damaging to neuronal cells. The assessment of tPA activity and PAI- may be useful for understanding the pathogenesis/ prognosis of MS and similar neurological diseases. We now use in situ hybridization and immunohistochemistry to localize tPA gene expression in tissue sections and are setting up mouse models to study the role of tPA in demyelinating disorders.
The action of antibodies, specific to membrane of sarcoplasmic reticulum, on the tonic tension (TT) development and sensitivity of the contractile proteins to Ca2’ of skied rat papillary muscles is investigated. It was shown that the antibodies in dose O,l-1,0 mg protein/ml evoke the additional increase in tonic tension on 3-5 min of the antibodies action. The increase run up to 40 % of initial values. The previous blockade of Ca2’ release from intracellular stores by ruthenium red and also its initiation by caffeine (ryanodme) removed the development of the tension oscillations. The increase of the antibody-dependent IT is not bound with growth of the sensitivity of contractile proteins to Ca ions, since the relations pCa2+--relative tension are not changed at various concentrations of Ca2+ and antibodies. These data demonstrate that one of reasons responsible for Ca2+ overload of cardiac myocytes during immunogenic damage is the antibody-dependent Ca2’ release from the sarcoplasmic reticulum pools.
138