Apolipoprotein E/APOE3 Protein, Human (HEK293, His)

Apolipoprotein E/ApoE3 is an apolipoprotein isoform that mediates lipid transport and plays a crucial role in lipid homeostasis in both plasma and the central nervous system by binding to LDL receptors (LDLR), LDL receptor-related proteins (LRP1, LRP2, LRP8), Very Low-Density Lipoprotein Receptor (VLDLR), and Heparin. The Apolipoprotein E/ApoE3 Protein, Human (HEK293, His) is a recombinant protein with a His tag at the N-terminus, consisting of 299 amino acids (K19-H317), and is expressed in HEK293 cells^[1].

Apolipoprotein E/APOE3 is an amphiphilic molecule that interacts with both the lipid core of lipoprotein particles and the aqueous environment of plasma^[3].
Apolipoprotein E/APOE3 regulates plasma and central nervous system lipid metabolism by binding to LDL receptor (LDLR), LDL receptor-related proteins (LRP1, LRP2, LRP8), and Very Low-Density Lipoprotein Receptor (VLDLR) as well as heparin (Heparin)^[9][10][12].
Apolipoprotein E/APOE3 first promotes HDL (high-density lipoprotein) synthesis by interacting with ABCA1 and then transports HDL from peripheral tissues to the liver, thereby clearing cholesterol from it. Apolipoprotein E/APOE3 plays an important role in regulating cholesterol homeostasis^[11].
Apolipoprotein E/APOE can bind to the immune cell receptor LILRB4 to modulate immune responses^[13].
Apolipoprotein E/APOE3 can activate MAP3K12 and atypical MAPK signaling pathways to enhance AP-1-mediated APP transcription^[14].

Apolipoprotein E/ApoE3 (Human) (3 μM, 24 hours) provides a certain degree of protection against the inflammatory response induced by β-Amyloid (1-42) (HY-P1388) in neonatal rat astrocytes (NRA)^[5].
Apolipoprotein E/ApoE3 (Human) (10 μg/mL, 48 hours) enhances Aβ synthesis in neurons derived from mouse embryonic fibroblasts (MEF)^[5].

Apolipoprotein E/ApoE3 (Human) enhances diet-induced hypercholesterolemia and atherosclerosis in transgenic C57BL/6J mice with the hAPOE3 allele-targeted replacement of the Apolipoprotein E gene^[6].
Apolipoprotein E/ApoE3 (Human) releases cholesterol extracellularly in astrocytes of hApoE3 transgenic mice by producing high-density lipoprotein (HDL)-like particles^[8].

Measured in a cell proliferation assay using SH-SY5Y cells.The ED₅₀ for this effect is ≤17.23 ng/mL, corresponding to a specific activity is ≥5.8×10⁴ units/mg.

• 
  Measured in a cell proliferation assay using SH-SY5Y cells.The ED₅₀ for this effect is 15.14 ng/mL.corresponding to a specific activity is 6.61×10⁴ units/mg.

Human

HEK293

C-6*His

P02649 (K19-H317)

348  [NCBI]

KVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH

Approximately 36-40 kDa due to the glycosylation.

• 
  Greater than 95% as determined by reducing SDS-PAGE.

Lyophilized powder

Lyophilized from a 0.2 μm filtered solution of 20 mM Tris-HCl, 5% Trehalose,5% Mannitol, 0.02% Tween80, pH 8.0 or 20 mM PB, 150 mM NaCl, pH 7.4 or PBS, pH 7.4, 8% trehalose.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Gong JS, et al. Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from humanApoE3 and ApoE4 knock-in mice. J Biol Chem. 2002 Aug 16;277(33):29919-26.  [Content Brief]

  [2]. Gong JS, et al. Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons. Mol Neurodegener. 2007 May 15;2:9.  [Content Brief]

  [3]. Hatters DM, et al. Apolipoprotein E structure: insights into function. Trends Biochem Sci. 2006 Aug;31(8):445-54.  [Content Brief]

  [4]. Wetterau JR, et al. Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains. J Biol Chem.  [Content Brief]

  [5]. Dorey E, et al. Apolipoprotein E Isoforms Differentially Regulate Alzheimer's Disease and Amyloid-β-Induced Inflammatory Response in vivo and in vitro. J Alzheimers Dis. 2017;57(4):1265-1279.  [Content Brief]

  [6]. Sullivan PM, et al. Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis. J Biol Chem.  [Content Brief]

  [7]. Huang Y W A, et al. ApoE2, ApoE3, and ApoE4 differentially stimulate APP transcription and Aβ secretion[J]. Cell, 2017, 168(3): 427-441. e21.  [Content Brief]

  [8]. Gong J S, et al. Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice[J]. Journal of Biological Chemistry, 2002, 277(33): 29919-29926.  [Content Brief]

  [9]. Sehayek E, et al. Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent cellular metabolism of human triglyceride-rich lipoproteins through the low density lipoprotein receptor pathway.  [Content Brief]

  [10]. Kowal RC, et al. Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5810-4.  [Content Brief]

  [11]. Ji ZS, et al. Heparan sulfate proteoglycans participate in hepatic lipaseand apolipoprotein E-mediated binding and uptake of plasma lipoproteins, including high density lipoproteins. J Biol Chem.  [Content Brief]

  [12]. Fagan AM, et al. Apolipoprotein E-containing high density lipoprotein promotes neurite outgrowth and is a ligand for the low density lipoprotein receptor-related protein. J Biol Chem. 1996 Nov 22;271(47):30121-5.  [Content Brief]

  [13]. Deng M, et al. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature. 2018 Oct;562(7728):605-609.  [Content Brief]

  [14]. Huang YA, et al. ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion. Cell. 2017 Jan 26;168(3):427-441.e21.  [Content Brief]