SREBP2-STARD4 is involved in synthesis of cholesteryl ester stimulated by mono-butyl phthalate in MLTC-1 cells

Environ Toxicol. 2020 Mar;35(3):377-384. doi: 10.1002/tox.22874. Epub 2019 Nov 9.

Abstract

Sterol is synthesized from cholesterol which is from the hydrolysis of stored cholesteryl esters. The process of maintaining cholesterol homeostasis is regulated by SREBP2-STARD4. Lots of researches demonstrated that male steroidogenesis could be interfered by di-n-butyl phthalate (DBP) or monobutyl phthalate (MBP). However, mechanisms of MBP exposure in this process have not been uncovered clearly. The objectiveof this study was to explore roles of SREBP2 and STARD4 in cholesteryl estersynthesis stimulated by MBP in mouse Leydig tumor cells (MLTC-1). MLTC-1 exposedto 10-8, 10-7, 10-6, 10-5 M MBP showed that levels of cholestery ester were increased significantly at 10-7 M MBP. Besides, cholesteryl ester synthesis stimulated by MBP was down-regulate when STARD4 or SREBP2 were inhibited. Activity of SREBP2 binding to the promoter of STARD4 was increased after MBP exposure. This study suggests that MBP can increase cholesteryl ester synthesis through SREBP2-STARD4 signal pathway in MLTC-1 cells.

Keywords: SREBP2; STARD4; cholesteryl ester; mono-butyl phthalate.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cholesterol Esters / biosynthesis*
  • Dibutyl Phthalate / pharmacology
  • Down-Regulation / drug effects
  • Male
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Phthalic Acids / pharmacology*
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects*
  • Sterol Regulatory Element Binding Protein 2 / antagonists & inhibitors
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Sterol Regulatory Element Binding Protein 2 / metabolism*

Substances

  • Cholesterol Esters
  • Membrane Transport Proteins
  • Phthalic Acids
  • RNA, Small Interfering
  • Srebf2 protein, mouse
  • Stard4 protein, mouse
  • Sterol Regulatory Element Binding Protein 2
  • Dibutyl Phthalate
  • monobutyl phthalate