|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2008-1-7
|
|
pubmed:abstractText |
DHCR24/seladin-1, a crucial enzyme in sterol synthesis, is of lower abundance in brain areas affected by Alzheimer's disease. While high levels of DHCR24/seladin-1 exert antiapoptotic function by conferring resistance against oxidative stress, the molecular mechanism for this protective effect is not fully understood. Here we show that DHCR24/seladin-1 expression is up-regulated in an acute response and down-regulated in a chronic response to oxidative stress. High levels of DHCR24/seladin-1 were associated with elevated cholesterol concentrations and a general increase in cholesterol biosynthesis upon oxidative stress exposure in neuroblastoma SH-SY5Y cells. DHCR24/seladin-1 overexpression conferred resistance to oxidative stress in a cholesterol-dependent manner. Mutating the reductase activity within DHCR24/seladin-1 abolished this protective effect. Conversely, DHCR24/seladin-1 levels diminished upon chronic exposure to oxidative stress. Low levels of DHCR24/seladin-1 were associated with reduced p53 levels, independent of DHCR24 activity and cholesterol concentrations. Additionally, ablation of DHCR24/seladin-1 prevented apoptosis of primary neurons in a p53-dependent manner and reduced the response of critical p53 targets due to deficient stabilization of p53 and therefore elevated p53 ubiquitination and degradation. Our findings reveal a dual capacity of DHCR24/seladin-1, which appears to be involved in two mechanistically independent prosurvival effects, exerting an acute response and a chronic response to oxidative stress.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-11007892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-11519011,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-12115731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-13671378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-14684813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-15001630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-15577914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-15585566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-15688385,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-15865932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16054061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16091489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16321981,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16407971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16513830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16565487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16754746,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16762343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-16901471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-1694094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-4911016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-7828854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-8402897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-8605870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-8643593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-9438241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-9657968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-9717713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17984220-9990098
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/DHCR24 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dhcr24 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases Acting on CH-CH...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
1098-5549
|
|
pubmed:author |
pubmed-author:BenvenutiSusannaS,
pubmed-author:CrameriAramesA,
pubmed-author:HeppnerFrank LFL,
pubmed-author:KälinRoland ERE,
pubmed-author:KuehnleKatrinK,
pubmed-author:KulicLukaL,
pubmed-author:LucianiPaolaP,
pubmed-author:MohajeriM HasanMH,
pubmed-author:NitschRoger MRM,
pubmed-author:PeriAlessandroA,
pubmed-author:RattiFrancescaF,
pubmed-author:RodolfoMonicaM
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
28
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
539-50
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:17984220-Animals,
pubmed-meshheading:17984220-Cell Survival,
pubmed-meshheading:17984220-Cells, Cultured,
pubmed-meshheading:17984220-Cholesterol,
pubmed-meshheading:17984220-Gene Expression Regulation,
pubmed-meshheading:17984220-Hydrogen Peroxide,
pubmed-meshheading:17984220-Mice,
pubmed-meshheading:17984220-Nerve Tissue Proteins,
pubmed-meshheading:17984220-Neurons,
pubmed-meshheading:17984220-Oxidative Stress,
pubmed-meshheading:17984220-Oxidoreductases Acting on CH-CH Group Donors,
pubmed-meshheading:17984220-RNA, Small Interfering,
pubmed-meshheading:17984220-Time Factors,
pubmed-meshheading:17984220-Tumor Suppressor Protein p53,
pubmed-meshheading:17984220-Ubiquitination
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress.
|
|
pubmed:affiliation |
Swiss Academy of Medical Sciences, Petersplatz 13, 4051 Basel, Switzerland. k.kuehnle@samw.ch
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
