Activation of Rac1 increases c-Jun NH2-terminal kinase activity and DNA fragmentation in a calcium-dependent manner in rat myoblast cell line H9c2

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Abstract

We examined the role of intracellular Ca2+ in c-Jun NH2-terminal kinase (JNK) activation and DNA fragmentation in the rat myoblast cell line H9c2 using small GTP-binding protein Rac1. A constitutively active mutant of Rac1 (V12-Rac1) increased JNK-responsive gene expression 6-fold, although this increase was attenuated by the intracellular Ca2+ chelator BAPTA-AM. V12-Rac1 also increased the number of DNA fragmentated cells. However, V12-Rac1-mediated JNK activation was not affected by BAPTA-AM as determined by direct measurement of active forms, and V12-Rac1 did not affect intracellular Ca2+ concentration. These results suggest that Rac1 can activate JNK and induces cell injury, but [Ca2+](i) is necessary for V12-Rac1 to induce DNA fragmentation downstream of JNK activation.

Original languageEnglish
Pages (from-to)350-354
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume262
Issue number2
DOIs
Publication statusPublished - Aug 27 1999
Externally publishedYes

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JNK Mitogen-Activated Protein Kinases
Myoblasts
DNA Fragmentation
Rats
Chemical activation
Cells
Calcium
Cell Line
DNA
rac1 GTP-Binding Protein
Chelating Agents
Gene expression
Gene Expression
Wounds and Injuries
1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Activation of Rac1 increases c-Jun NH2-terminal kinase activity and DNA fragmentation in a calcium-dependent manner in rat myoblast cell line H9c2",
abstract = "We examined the role of intracellular Ca2+ in c-Jun NH2-terminal kinase (JNK) activation and DNA fragmentation in the rat myoblast cell line H9c2 using small GTP-binding protein Rac1. A constitutively active mutant of Rac1 (V12-Rac1) increased JNK-responsive gene expression 6-fold, although this increase was attenuated by the intracellular Ca2+ chelator BAPTA-AM. V12-Rac1 also increased the number of DNA fragmentated cells. However, V12-Rac1-mediated JNK activation was not affected by BAPTA-AM as determined by direct measurement of active forms, and V12-Rac1 did not affect intracellular Ca2+ concentration. These results suggest that Rac1 can activate JNK and induces cell injury, but [Ca2+](i) is necessary for V12-Rac1 to induce DNA fragmentation downstream of JNK activation.",
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T1 - Activation of Rac1 increases c-Jun NH2-terminal kinase activity and DNA fragmentation in a calcium-dependent manner in rat myoblast cell line H9c2

AU - Nishida, Motohiro

AU - Nagao, Taku

AU - Kurose, Hitoshi

PY - 1999/8/27

Y1 - 1999/8/27

N2 - We examined the role of intracellular Ca2+ in c-Jun NH2-terminal kinase (JNK) activation and DNA fragmentation in the rat myoblast cell line H9c2 using small GTP-binding protein Rac1. A constitutively active mutant of Rac1 (V12-Rac1) increased JNK-responsive gene expression 6-fold, although this increase was attenuated by the intracellular Ca2+ chelator BAPTA-AM. V12-Rac1 also increased the number of DNA fragmentated cells. However, V12-Rac1-mediated JNK activation was not affected by BAPTA-AM as determined by direct measurement of active forms, and V12-Rac1 did not affect intracellular Ca2+ concentration. These results suggest that Rac1 can activate JNK and induces cell injury, but [Ca2+](i) is necessary for V12-Rac1 to induce DNA fragmentation downstream of JNK activation.

AB - We examined the role of intracellular Ca2+ in c-Jun NH2-terminal kinase (JNK) activation and DNA fragmentation in the rat myoblast cell line H9c2 using small GTP-binding protein Rac1. A constitutively active mutant of Rac1 (V12-Rac1) increased JNK-responsive gene expression 6-fold, although this increase was attenuated by the intracellular Ca2+ chelator BAPTA-AM. V12-Rac1 also increased the number of DNA fragmentated cells. However, V12-Rac1-mediated JNK activation was not affected by BAPTA-AM as determined by direct measurement of active forms, and V12-Rac1 did not affect intracellular Ca2+ concentration. These results suggest that Rac1 can activate JNK and induces cell injury, but [Ca2+](i) is necessary for V12-Rac1 to induce DNA fragmentation downstream of JNK activation.

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