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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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A Subset of Caveolin-1 Interacts with a Fraction of Acyl-CoA:Cholesterol Acyltransferase 1 (ACAT1/SOAT1) at an Endoplasmic Reticulum Subdomain to Attenuate Cholesteryl Ester Biosynthesis.

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Enzymatically Formed Oxysterols and Cell Death.

Yasuomi Urano1, Noriko Noguchi2

  • 1Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto, Japan. yurano@mail.doshisha.ac.jp.

Advances in Experimental Medicine and Biology
|November 30, 2023
PubMed
Summary

Side-chain oxysterols, produced from cholesterol, are vital signaling molecules regulating cholesterol balance. Disruptions in these oxysterols are linked to human diseases and influence cell death pathways.

Keywords:
24(S)-hydroxycholesterol25-hydroxycholesterol27-hydroxycholesterolAcyl-CoA:cholesterol acyltransferaseCell deathEndoplasmic reticulumIntegrated stress responseLiver X receptorSide-chain oxysterolsSterol regulatory element-binding protein

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathophysiology

Background:

  • Cholesterol metabolism involves enzymatic side-chain hydroxylation, producing various oxysterols.
  • Side-chain oxysterols like 24(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol are key intermediates in bile acid synthesis.
  • These oxysterols function as crucial signaling molecules in maintaining cholesterol homeostasis within cells.

Purpose of the Study:

  • To provide a comprehensive overview of the pathophysiological roles of side-chain oxysterols in human diseases.
  • To summarize the molecular mechanisms by which side-chain oxysterols induce different forms of cell death.
  • To highlight the implications of oxysterol imbalance in disease development.

Main Methods:

  • Literature review and synthesis of existing research on side-chain oxysterols.
  • Analysis of studies investigating the signaling functions of oxysterols.
  • Examination of research on oxysterol-mediated cell death induction.

Main Results:

  • Side-chain oxysterols are implicated in the pathophysiology of various human diseases due to dysregulated homeostasis.
  • Oxysterols exhibit significant effects on cellular proliferation and can trigger cell death.
  • Specific molecular pathways mediating oxysterol-induced cytotoxicity have been identified.

Conclusions:

  • Dysregulation of side-chain oxysterol homeostasis is a critical factor in the development of human diseases.
  • Understanding the mechanisms of oxysterol-induced cell death is essential for therapeutic interventions.
  • Further research into oxysterol signaling and metabolism holds promise for treating cholesterol-related disorders.