본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Experimental cell research v.361 no.1, 2017년, pp.178 - 191   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

The viability of primary hepatocytes is maintained under a low cysteine-glutathione redox state with a marked elevation in ophthalmic acid production

Lee, Jaeyong (Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan ) ; Kang, Eun Sil (Sanghuh College of Life Sciences, Konkuk University, Republic of Korea ) ; Kobayashi, Sho (Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan ) ; Homma, Takujiro (Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan ) ; Sato, Hideyo (Laboratory of Biochemistry and Molecular Biology, Department of Medical Technology, Faculty of Medicine, Niigata University, Japan ) ; Seo, Han Geuk (Sanghuh College of Life Sciences, Konkuk University, Republic of Korea ) ; Fujii, Junichi (Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan ) ;
  • 초록  

    Abstract Extracellular cystine, the oxidized form of cysteine (Cys), is taken up by cells via the cystine transporter xCT. xCT is not expressed in the liver but is induced in primary hepatocytes under conventional cultured conditions. However, compared to wild-type hepatocytes those from the xCT-knockout mouse showed no evidence of an abnormality and the levels of both Cys and glutathione (GSH) remained unchanged. The levels of ophthalmic acid (OPT), which is produced as an alternative compound by the GSH-synthesizing pathway, became increased during the culturing of hepatocytes. It therefore appears that, in primary hepatocytes, Cys is provided by systems other than xCT, most likely via the transsulfuration pathway, but the levels that are produced are not sufficient. We also employed mouse hepatoma-derived Hepa1-6 cells, which constitutively express xCT. When Hepa 1-6 cells were cultivated in Cys-free media, the levels of intracellular Cys and GSH were decreased, compared to cells cultured in conventional media, leading to cell death accompanied by an increase in the levels of reactive oxygen species and lipid peroxidation products with characteristics similar to ferroptosis. While OPT levels were increased by only to a limited extent in Hepa 1-6 cells, primary hepatocytes cultured in Cys- and Met-free media showed a marked elevation in OPT, reaching levels nearly equivalent to the GSH levels when the cells were cultured in conventional media. Thus, OPT may become a marker for Cys insufficiency and might be used to predict pathological conditions of cells with elevated oxidative stress. Highlights xCT is induced in primary mouse hepatocytes under culture conditions. xCT-KO hepatocytes contained normal levels of cysteine and glutathione (GSH). Primary hepatocytes were viable in cysteine- and methionine-free media. Ophthalmic acid levels were equivalent to those of GSH in hepatocytes. Graphical abstract Differential cysteine-supply systems between the primary mouse hepatocytes and Hepa 1-6 cells under conventional or Cys/Met-free culture. Met; Methionine, Hcy; Homocysteine, Cst; Cystathionine, Cys; Cysteine, Thr; Threonine, Glu; Glutamate, 2OB; 2-Oxo-butyric acid, 2AB; 2-Amino-butyric acid, GSH; Glutathione, OPT; Ophthalmic acid, γGCS; γ-Glutamylcysteine synthetase, GS; Glutathione synthetase; NAAT; neutral amino acid transporter [DISPLAY OMISSION]


  • 주제어

    Cysteine .   Cystine .   xCT .   Glutathione .   Ophthalmic acid .   Autophagy.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기