title: PCSK9 Promotes oxLDL-Induced PC12 Cell Apoptosis Through the Bcl-2/Bax-Caspase 9/3 Signaling Pathway.
abstract: Hyperlipidemia is a risk factor for neurodegenerative diseases. Proprotein convertase subtilisin / Kexin type 9 (PCSK9) degrades hepatic low-density lipoprotein receptor (LDLR) to regulate lipid metabolism. It is unclear if PCSK9 plays a role in neurodegenerative diseases.
  
  
  
  This study was designed to determine whether PCSK9 is crucial between hyperlipidemia and Alzheimer's disease. The interrelationship between PCSK9 and neuronal apoptosis was explored in PC12 cells in response to treatment with oxidized low-density lipoprotein (oxLDL).
  
  
  
  Cultured PC12 cells were serum-starved and incubated with different concentrations of oxLDL for 24 h. Intracytoplasmic lipid droplets were observed by oil red O staining. Morphological assessment of apoptotic cells was performed using Hoechst 33258 staining and flow cytometry analysis. The expression of mRNA and protein was detected by reverse-transcription polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Transfection of small interfering RNA (siRNA) into PC12 cells was conducted using HiperFect Transfection Reagent. Concentrations of Aβ40 and Aβ42 were detected by enzyme-linked immunosorbent assay (ELISA) kit.
  
  
  
  Intracellular lipid content, the number of apoptotic cells, and PCSK9 expression were increased in PC12 cells after oxLDL treatment. Transfection with PCSK9 siRNA reduced the oxLDL-induced apoptosis of PC12 cells. We further confirmed the involvement of Bcl-2/Bax-Caspase (9, 3) signaling pathway in the regulation of PC12 cells apoptosis.β-Secretase 1, another target gene of PCSK9, was downregulated in PC12 cells in response to oxLDL treatment. Aβ40 and Aβ42 contents were also decreased.
  
  
  
  PCSK9 promotes oxLDL-induced PC12 cell apoptosis through the Bcl-2/Bax-Caspase 9/3 signaling pathway.
authors.forename: Lu-Shan
authors.initials: LS
authors.lastname: Liu
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Bai
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ren
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Pan
authors.forename: Ni-Ya
authors.initials: NY
authors.lastname: He
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.forename: Zhi-Han
authors.initials: ZH
authors.lastname: Tang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism; D000071449:Proprotein Convertase 9 / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016895:Culture Media, Serum-Free; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; C099252:oxidized low density lipoprotein; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D020169:Caspases
keywords: Amyloid β peptide; PC12 cell; apoptosis; caspases; oxidized low-density lipoprotein; proprotein convertase subtilisin/kexin type 9; signal pathway; β-site AβPP cleaving enzyme 1