CADMIUM INTERFERES WITH <Ca^(2+)> -REGULATED CELLULAR FUNCTIONS
| Project/Area Number |
60480464
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
IMURA NOBUMASA SCHOOL OF PHARMACEUTICAL SCIENCES, KITASATO UNIVERSITY, PROF. DEP. OF PUBLIC HEALTH,, 薬学部, 教授 (70012606)
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| Co-Investigator(Kenkyū-buntansha) |
SEKO YOSHIYUKI SCHOOL OF PHARMACEUTICAL SCIENCES, KITASATO UNIVERSITY, RES. ASSOC. DEP. OF PUBL, 薬学部, 助手 (60133360)
MIURA KYOKO FACULTY OF ECONOMICS, WAKO UNIVERSITY, ASSOC. PROF. DEP. OF ENVIRN, SCI., 経済学部, 助教授 (70101293)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1986: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1985: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Cadmium / Calmodulin / cAMP-phosphodiesterase / Myosin-ATPase / Sarcoplasmic reticulum vesicles / Ca,Mg-ATPase |
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| Research Abstract |
EFFECTS OF Cd ON Ca-CALMODULIN DEPENDENT ENZYME (3',5'-CYCLIC AMP PHOSPHODIESTERASE, cAMP-PDE), Ca DEPENDENT BUT CALMODULIN INDEPENDENT ENZYME (MYOSIN-ATPase) AND Ca,Mg-ATPase, WHICH PLAY IMPORTANT ROLES IN THE REGULATION OF CELL FUNCTIONS MEDIATED BY Ca, WERE STUDIED.
1. EFFECTS OF Cd ON THE ACTIVITY OF cAMP-PDE AND MYOSIN-ATPase.
IN THE ABSENCE OF Ca, cAMP-PDE WAS ACTIVATED BY Cd AT CONCENTRATIONS RANGING FROM <10^(-6)> M TO 5 x <10^(-5)> M IN WHICH THE ACTIVATION RATE INCREASED AS Cd CONCENTRATION INCREASED. IN THE PRESENCE OF Ca, THE INCREASE IN ENZYME ACTIVITY OBSERVED ON ADDITION OF Cd WAS ADDITIVE TO THAT CAUSED BY Ca ALONE UP TO A Cd CONCENTRATION OF ABOUT <10^(-5)> M. ELECTROPHORETIC MIGRATION OF CALMODULIN INCUBATED WITH Cd ON SDS-POLYACRYLAMIDE GELS INDICATED THAT Cd EXERTS CONFORMATIONAL CHANGES IN THE CALMODULIN MOLECULE IN THE SAME MANNER AS THAT OF Ca. FURTHER, THE BINDING OF Ca TO CALMODULIN WAS EFFICIENTLY INHIBITED BY EQUIMOLAR AMOUNT OF Cd. FROM THESE RESULTS IT WAS CO
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NCLUDED THAT THE ACTIVATION OF cAMP-PDE BY Cd IS CAUSED BY Cd-CALMODULIN COMPLEX. IN ADDITION, Cd WAS FOUND TO BE ABLE TO SUBSTITUTE FOR Ca TO ACTIVATE Ca DEPENDENT MYOSIN-ATPase AS WELL AS THE CASE OF CALMODULIN DEPENDENT cAMP-PDE.
2. EFFECTS OF Cd ON Ca UPTAKE BY SARCOPLASMIC RETICULUM VESICLES (SRV) PREPARED FROM RABBIT SKELETAL MUSCLES.
Cd AT CONCENTRATION OF 3 x <10^(-6)> M - 5 x <10^(-5)> M COMPETITIVELY BLOCKED THE Ca UPTAKE BY SRV. THE 50 % INHIBITION WAS CAUSED WITH <10^(-5)> M Cd IN THE PRESENCE OF <10^(-5)> M Ca. Cd DID NOT SHOW ANY DISCERNIBLE EFFECTS ON RELEASE OF Ca FROM Ca PRELOADED SRV BELOW <10^(-5)> M. EITHER Ca,Mg-ATPase ACTIVITY NOR PHOSPHOENZYME (EP) FORMATION WAS NOT AFFECTED BY Cd UP TO <10^(-5)> M. FURTHER, THE AMOUNT OF Cd TAKEN UP BY SRV COULD NOT ACCOUNT FOR THE DECREASE IN Ca UPTAKE CAUSED BY Cd. FROM THESE RESULTS IT IS CONCLUDED THAT Cd COULD BIND TO Ca BINDING SITE ON Ca,Mg-ATPase, STIMULATE THE ENZYME TO HYDROLISE ATP AND FORM EP, BUT NOT TRANSPORT ITSELF IN STEAD OF Ca. THUS Cd INHIBITS Ca TRANSPORT INTO SRV AND CONSUMES ATP IN VAIN.
THE STIMULATION OF Ca-DEPENDENT ENZYMES AND INHIBITION OF Ca TRANSPORT BY Cd MAY ALTER THE Ca-REGULATED CELLULAR FUNCTIONS TO EXERT ADVERSE EFFECTS ON THE CELLS. Less
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