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1991 Fiscal Year Final Research Report Summary

Cytosolic free calcium and intracellular pH in ischemic and drug-induced acute renal failure.

Research Project

Project/Area Number 01570366
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionJichi Medical School

Principal Investigator

ASANO Yasushi  Jichi Medical School, Department of Medicine, Professor., 医学部, 教授 (00050500)

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)
Project Period (FY) 1989 – 1991
KeywordsIshemic acute / Drug-induced nephrotoxicity / Cytorolic-free calcium / Intracellular pH / Superoxide
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%)

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Takeda K.,Ohara T.,Tabei K.and Asano Y.: "Dual regulatory mechanisms of proton transport in rat papillary collecting duct cells in culture." Jpn.J.Physiol.39. 397-410 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Muto S.,Furuya H.,Tabei K.and Asano Y.: "Site and mechanism of action of epidermal growth factor in rabbit cortical collecting duct." Am.J.Physiol.260. F163-F169 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara T.,Takeda K.,and Asano Y.: "Stimulation of Na^+/H^+ exchange induced by angioteusin II in rat cultured voscular smooth muscle cells:role of Ca^<2+> and C-Kinase." Jpn.Circ.J.56. 133-141 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara T.,Takeda K.and Asano Y.: "Intracellular pH regulatory mechanisms in inner medullary collecting duct cells in culture:role of Ca^<2+>,cAMP and protein Kinase C."

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda K.,Terao N.Ohara T.and Asano Y.: "Oxidative stress in cultured rat inner medullary duct cells."

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara T.,Takeda K.,Tabei K.,and Asano Y.: "Effect of ATP depletion on intracellular pH and cytasolic free calcium in rat inner medullary collecting duct cells."

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeda K., Ohara T., Tabei K., and Asono Y.: "Dual regulatory mechanisms of proton transport in rat papillary collecting duct cells in culture." Jpn. J. Physid.39. 397-410 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Muto S., Faruya H., Tabei K. and Asano Y.: "Site and mechanism of action of epidermal growth factor in rabbit cortical collecting duct." Am. J. Physiol.260. F163-F169 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara T., Takeda K, and Asano Y.: "Stimulation of Na^+/H^+ exchange induced by angiotensin II in rat cultured vascular smooth muscle cells : role of Ca^<2+> and C-kinase" Jpn. Circ. J.56. 133-141 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara T., Takeda K. and Asano Y.: "Intracellular pH regulatory mechanisms in inner medullary collecting duct cells in culture : role of Ca^<2+>, cAMP and Protein Kinase C."

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeda, K., Terao N., Ohara T., and Asano Y.: "Oxidative stress in cultured rat inner medullany duct cells."

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara T., Takeda K., Tabei K. and Asano Y.: "Effect of ATP depletion o intracellular pH and Cytosolic free calcium in rat inner medullary collecting duct cells."

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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