title: side-chain-oxidized oxysterols upregulate ACE2 and Mas receptor in rat primary neurons.
abstract: BACKGROUND
  Disturbances in cholesterol metabolism have been associated with hypertension and Alzheimer's disease (AD). We recently reported increased angiotensin-converting enzyme (ACE) activity and angiotensinogen (AGT) levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and AD. ACE activity positively correlated with plasma and CSF 27-hydroxycholesterol (27-OH) levels, an oxysterol that passes to the brain from the blood. Additionally, we showed that 27-OH and 24(S)-hydroxycholesterol (24S-OH) enhance AGT synthesis and modulate renin and ACE activities in brain cells.
  
  
  OBJECTIVE
  To gain insight into how oxysterols affect the brain renin-angiotensin system (RAS), we analyzed the effects of 24S-OH and 27-OH on two other proteins in this system: ACE2 and Mas receptor (MasR).
  
  
  METHODS
  RT-PCR and Western blot analysis in rat primary neurons treated with either 24S-OH or 27-OH.
  
  
  RESULTS
  The levels of ACE2 and MasR were increased by a physiological concentration (1 μM) of these oxysterols after 24 h.
  
  
  CONCLUSIONS
  24S-OH and 27-OH enhance the brain RAS by acting on different levels, from the precursor to several downstream enzymes. Our results support the idea that disturbances in cholesterol metabolism would contribute to alterations in the brain RAS, which further suggest mechanistic links between two well-known risk factors for AD: hypercholesterolemia and hypertension.
authors.affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Alzheimer's Disease Research Center, Stockholm, Sweden.
authors.forename: Laura
authors.initials: L
authors.lastname: Mateos
authors.forename: Muhammad-Al-Mustafa
authors.initials: MA
authors.lastname: Ismail
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Angel
authors.initials: A
authors.lastname: Cedazo-Mínguez
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D006888:Hydroxycholesterols / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D006888:Hydroxycholesterols; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2