| Project/Area Number |
01570366
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Jichi Medical School |
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Principal Investigator |
ASANO Yasushi Jichi Medical School, Department of Medicine, Professor., 医学部, 教授 (00050500)
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| Co-Investigator(Kenkyū-buntansha) |
HOMMA Sumiko Jichi Medical Shcool, Department of Medicine, Instructor,, 医学部, 助手 (70209336)
MUTO Shigeaki Jichi Medical School, Department of Medicine, Instructor,, 医学部, 助手 (40190855)
TAKEDA Katsuji Jichi Medical School, Department of Medicine, Assistant P.,, 医学部, 講師 (10102253)
TABEI Kaoru Jichi Medical School, Department of Medicine, Assistant P.,, 医学部, 講師 (90155234)
KUSANO Eiji Jichi Medical School, Department of Medicine, Assistant P.,, 医学部, 講師 (50102249)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Ishemic acute / Drug-induced nephrotoxicity / Cytorolic-free calcium / Intracellular pH / Superoxide |
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| Research Abstract |
1. Cytosolic free calcium ([Ca^<2+>]i) and intracellular pH(pHi) during cell ischemia
The effect of ischemia on [Ca^<2+>]i and pHi was determined in cultured rat inner medullary collecting duct (IMCD) cells exposed to NaCN (5mM) and 2-deoxy-D-glucose (5mM). After the addition of cyanide plus 2-deoxy-D-glucose, [Ca^<2+>]i rose and pHi decreased (DELTApH=-0.35). Verapamil (10^<-4>M) or EGTA (2mM) significantly blunted the rise in [Ca^<2+>]i, and decreased pHi moreover (DELTApH=-0.65). Lowering extracellular pH from 7.8 to 6.4 inhibited the rise in [Ca^<2+>]i induced by metabobic inhibitors. At pH 6.5, or with verapamil IMCD cells were protected against ischemic injury as compared with cells incubated at pH 7.4.
2. Effect of cyclosporin on [Ca^<2+>]i.
Cyclosporin (10^<-8>M) had no effect on [Ca^<2+>]i in LLC-PK, cells.
3. Oxidative stress in cultured rat IMCD cells : role of Ca^<2+>.
Tert-Butyl Hydroperoxide (TBHP) (5mM) increased [Ca^<2+>]i and reduced IMCD cells viability to 26i, <plus-minus>8.9% at 60min. The increase in [Ca^<2+>]i induced by TBHP was significantly inhibited by EGTA (2mM) or verapamil (10^<-4>M). Both EGTA and verapamil provided significant protection (cell viability. TBHP+EGTA : 61.7<plus-minus>13.1%, TBHP + verapamil : 64.7<plus-minus>5.5%, TBHP : 26.7 <plus-minus>8.9%. P<0.001>. Lowering extracellular pH from 7.4 to 6.6 blunted the rise in [Ca^<2+>] induced by TBHP and protected cell injury (Cell viability. at pH 6.6 : 66.2 <plus-minus> 15.7%)
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