Arachidonate 12S-lipoxygenase of platelet-type in hepatic stellate cells of methionine and choline-deficient diet-fed mice

J Biochem. 2020 Nov 1;168(5):455-463. doi: 10.1093/jb/mvaa062.


A role of 12-lipoxygenase in the progression of non-alcoholic steatohepatitis (NASH) is suggested, although the underlying mechanism is not entirely understood. The catalytic activity of 12S-lipoxygenase that was hardly observed in liver cytosol of normal chow-fed mice was clearly detectable in that of NASH model mice prepared by feeding a methionine and choline-deficient (MCD) diet. The product profile, substrate specificity and immunogenicity indicated that the enzyme was the platelet-type isoform. The expression levels of mRNA and protein of platelet-type 12S-lipoxygenase in the liver of MCD diet-fed mice were significantly increased compared with those of normal chow-fed mice. Immunohistochemical analysis showed that platelet-type 12S-lipoxygenase colocalized with α-smooth muscle actin as well as vitamin A in the cells distributing along liver sinusoids. These results indicate that the expression level of platelet-type 12S-lipoxygenase in hepatic stellate cells was increased during the cell activation in MCD diet-fed mice, suggesting a possible role of the enzyme in pathophysiology of liver fibrosis.

Keywords: arachidonic acid; hepatic stellate cells; non-alcoholic steatohepatitis (NASH); platelet-type 12S-lipoxygenase; α-smooth muscle actin.

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / genetics
  • Arachidonate 12-Lipoxygenase / metabolism*
  • Choline / metabolism*
  • Choline Deficiency / metabolism
  • Diet / adverse effects*
  • Disease Models, Animal
  • Hepatic Stellate Cells / enzymology*
  • Isoenzymes
  • Liver / enzymology*
  • Male
  • Methionine / deficiency*
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology*


  • Isoenzymes
  • Methionine
  • Arachidonate 12-Lipoxygenase
  • Choline