RISS 학술연구정보서비스

검색
다국어 입력

http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.

변환된 중국어를 복사하여 사용하시면 됩니다.

예시)
  • 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
  • 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
닫기
    인기검색어 순위 펼치기

    RISS 인기검색어

      SCI SCIE SCOPUS

      Protein kinase Cδ knockout mice are protected from cocaine-induced hepatotoxicity

      한글로보기

      https://www.riss.kr/link?id=A107454315

      • 0

        상세조회
      • 0

        다운로드
      서지정보 열기
      • 내보내기
      • 내책장담기
      • 공유하기
      • 오류접수

      부가정보

      다국어 초록 (Multilingual Abstract)

      <P><B>Abstract</B></P> <P>We investigated whether protein kinase Cδ (PKCδ) mediates cocaine-induced hepatotoxicity in mice. Cocaine treatment (60 mg/kg, i.p.) significantly increased cleaved PKCδ expression in the liver of wild-type (WT) mice, and led to significant increases in oxidative parameters (i.e., reactive oxygen species, 4-hydroxylnonenal and protein carbonyl). These cocaine-induced oxidative burdens were attenuated by pharmacological (i.e., rottlerin) or genetic depletion of PKCδ. We also demonstrated that treatment with cocaine resulted in significant increases in nuclear factor erythroid-2-related factor 2 (Nrf-2) nuclear translocation and increased Nrf-2 DNA-binding activity in wild-type (WT) mice. These increases were more pronounced in the rottlerin-treated WT or PKCδ knockout mice than in the saline-treated WT mice. Although cocaine treatment increased Nrf-2 nuclear translocation, DNA binding activity, and γ-glutamyl cysteine ligases (i.e., GCLc and GCLm) mRNA expressions, while it reduced the glutathione level and GSH/GSSG ratio. These decreases were attenuated by PKCδ depletion. Cocaine treatment significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum of WT mice signifying the hepatic damage. These increases were also attenuated by PKCδ depletion. In addition, cocaine-induced hepatic degeneration in WT mice was evident 1 d post-cocaine. At that time, cocaine treatment decreased Bcl-2 and Bcl-xL levels, and increased Bax, cytosolic cytochrome c, and cleaved caspase-3 levels. Pharmacological or genetic depletion of PKCδ significantly ameliorated the pro-apoptotic properties and hepatic degeneration. Therefore, our results suggest that inhibition of PKCδ, as well as activation of Nrf-2, is important for protecting against hepatotoxicity induced by cocaine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cocaine induces hepatotoxicity via oxidative stress and activation of PKCδ. </LI> <LI> Depletion of PKCδ protects from cocaine-induced hepatotoxicity. </LI> <LI> Depletion of PKCδ exerts antioxidant activity via Nrf2-related glutathione system. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
      번역하기

      <P><B>Abstract</B></P> <P>We investigated whether protein kinase Cδ (PKCδ) mediates cocaine-induced hepatotoxicity in mice. Cocaine treatment (60 mg/kg, i.p.) significantly increased cleaved PKCδ expres...

      <P><B>Abstract</B></P> <P>We investigated whether protein kinase Cδ (PKCδ) mediates cocaine-induced hepatotoxicity in mice. Cocaine treatment (60 mg/kg, i.p.) significantly increased cleaved PKCδ expression in the liver of wild-type (WT) mice, and led to significant increases in oxidative parameters (i.e., reactive oxygen species, 4-hydroxylnonenal and protein carbonyl). These cocaine-induced oxidative burdens were attenuated by pharmacological (i.e., rottlerin) or genetic depletion of PKCδ. We also demonstrated that treatment with cocaine resulted in significant increases in nuclear factor erythroid-2-related factor 2 (Nrf-2) nuclear translocation and increased Nrf-2 DNA-binding activity in wild-type (WT) mice. These increases were more pronounced in the rottlerin-treated WT or PKCδ knockout mice than in the saline-treated WT mice. Although cocaine treatment increased Nrf-2 nuclear translocation, DNA binding activity, and γ-glutamyl cysteine ligases (i.e., GCLc and GCLm) mRNA expressions, while it reduced the glutathione level and GSH/GSSG ratio. These decreases were attenuated by PKCδ depletion. Cocaine treatment significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum of WT mice signifying the hepatic damage. These increases were also attenuated by PKCδ depletion. In addition, cocaine-induced hepatic degeneration in WT mice was evident 1 d post-cocaine. At that time, cocaine treatment decreased Bcl-2 and Bcl-xL levels, and increased Bax, cytosolic cytochrome c, and cleaved caspase-3 levels. Pharmacological or genetic depletion of PKCδ significantly ameliorated the pro-apoptotic properties and hepatic degeneration. Therefore, our results suggest that inhibition of PKCδ, as well as activation of Nrf-2, is important for protecting against hepatotoxicity induced by cocaine.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cocaine induces hepatotoxicity via oxidative stress and activation of PKCδ. </LI> <LI> Depletion of PKCδ protects from cocaine-induced hepatotoxicity. </LI> <LI> Depletion of PKCδ exerts antioxidant activity via Nrf2-related glutathione system. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      더보기

      분석정보

      View

      상세정보조회

      0

      Usage

      원문다운로드

      0

      대출신청

      0

      복사신청

      0

      EDDS신청

      0

      동일 주제 내 활용도 TOP

      더보기

      주제

      연도별 연구동향

      연도별 활용동향

      연관논문

      연구자 네트워크맵

      공동연구자 (7)

      유사연구자 (20) 활용도상위20명

      이 자료와 함께 이용한 RISS 자료

      나만을 위한 추천자료

      해외이동버튼