CD36

Asociované choroby

AD

• Associated with the AD (Armesilla and Vega, 1994)
• In the brain, this glycoprotein is expressed on various cells
• Microglia, astrocytes
• Neurons
• Linked with
• Activation of immune system
• Removal of debris
• Mainly done by induction of apoptosis [1]

Obezita

Makulární degenerace věkem podmíněná

• Associated with age-related macular degeneration (AMD)
• CD36 expressed in the retinal pigment epithelium (RPE)
• Responsible for maintaining the integrity of Bruch’s membrane
• Preservation of visual functions
• CD36 deficient animals
• Oxidized LDL accumulated subretinally
• Decrease in permeability of Bruch’s membrane
• Impairment of the visual function (Picard et al., 2010) [1]

Diabetes type 2

• Increased expression of CD36 in high glucose concentration (Sun et al., 2010)
• Rats to the high-fat diet
• Effect of relocation the CD36 to the sarcolemma
• Increase of fatty acids intake occurs
• Dysfunction of the heart contractions
• Obese and type 2 diabetic patients
• Higher fatty acids transport into skeletal muscle
• Connected with the relocation of CD36 into the sarcolemma
• Probably also responsible for the insulin resistance
• Caused by some alterations in signalling cascades which leads to permanent relocation of CD36 into the sarcolemma
• Esterification into triacylglycerols, and higher concentrations of diacylglycerol and ceramides.
• Reduce the glucose uptake
• Beginning of the insulin resistance [1]
• Inhibition of CD36 present at sarcolemma
• Modulation of subcellular recycling of CD36 (Glatz et al., 2013) [1]

Steatoza jater

• Alcoholism and alcoholic steatosis associated with CD36
• CD36 had been reported higher in liver exposed to alcohol
• CD36 deficiency
• Protective role in the development of alcoholic steatosis
• Lipogenic resistance even though consuming a high-carbohydrate liquid diet (Clugston et al., 2014)

Nádory

• Anti-angiogenic and pro-apoptotic role
• Other demonstrated pro-tumorigenic role in cancer stem cells (Hale et al., 2014)
• Fatty acid uptake of cancerous cells
• Often modified, as they need to sustain their growth and proliferation
• CD36 functiong as a fatty acid translocase
• Modification of its expression may be involved.
• High free fatty acid levels
• May activate epithelial-mesenchymal transition by CD36 had been proposed
• Role in the progression of cancer (Nath et al., 2015)
• Angiogenesis
• Mediation of angiogenic activity
• Mostly its inhibition
• Expressed on microvascular endothelial cells
• Region of CD36 known as the CLESH domain
• Interacts with anti-angiogenic protein
• Thrombospondins-1 and -2
• Induces complex intracellular signalling cascade resulting in apoptosis
• Inhibition of microvascular endothelial cell migration, proliferation and tube formation
• Deletion of CD36 in mice
• Larger tumours
• Increased vascularity (Hale et al., 2012).

Plasmodium falciparum malaria and CD36

• Africa having the highest frequency of CD36 deficiency
• CD36 deficiency
• More serious progress of malaria than non-deficient people
• In patients with malaria it is responsible for nonopsonic phagocytosis of P. falciparum-infected erythrocytes
• By the blocking the CD36, the uptake of parasitized erythrocytes and nonopsonic phagocytosis can be inhibited
• Pharmacologic inhibition of CD36 signalization
• Reduction of phagocytosis of parasitized erythrocytes (Baruch et al., 1997) [1]

CD36 deficiency

• Described in humans
• Two subtypes based on the phenotype

Type I deficiency

• Does not express CD36 in either platelets or monocytes
• 10% of the deficiencies
• Associated with one of the many polymorphisms of CD36

Type II deficiency

• About 90% of cases
• CD36 is expressed only in monocytes and not in platelets
• More than 20 variants of CD36 had been identified
• CD36 consists of a relatively conservative zone and quite polymorphic coding zones
• Europeans having the lowest frequency
• Asian and African populations having the highest (Xu et al., 2014) [1]

Exprese

• Various cells all over the organism
• Platelets,
• Monocytes,
• Few endothelial cells,
• Mammary epithelial cells,
• Adipocytes,
• Activated keratinocytes,
• Erythrocytes
• Few tumour cell lines
• Specific for each tissue
• May vary
• During the differentiation of various cell types
• Some disorders
• Myeloproliferative disease [1]

CD36 Various functions

Retence v kostní dřeni

• Immature cell retention in bone marrow

Chuť tuku na jazyku

• Oral fat sensing
• Expression of CD36 in the apical cells of the taste bud
• Associated with the gustatory perception of dietary lipids
• Linked to the single nucleotide polymorphism (SNP) rs1761667
• A-allele of rs1761667 had been linked with the decreased oral sensitivity to oleic acid
• A-allele connected to the increased detection threshold of oleic acid
• Higher frequency in obese children than in lean (Daoudi et al.,2015) [1]

Fagocytoza

• Macrophages mediated ingestion of apoptotic neutrophils

Adheze

• Aggregation of platelets by interacting with platelet-agglutinating protein p37
• Mediator of few adhesive properties of the erythrocytes infected
• By Plasmodium falciparum to the postcapillary venular endothelium
• Receptor for
• Glycoprotein thrombospondin
• Collagen types 1 and 4

Transport MK

• Associated with the transport of long-chain fatty acids

Binding to the oxidized low-density lipoprotein

• Type B scavenger receptor
• Bind and internalize modified LDL particles
• Oxidized low-density lipoprotein (oxidized LDL)
• CD36-transfected cells
• Bind to the lipid part of oxidized LDL
• Binding can be inhibited by
• Anionic phospholipid vesicles
• Anti-CD36 antibodies
• The uptake of oxidized LDL
• Can lead to the development of macrophage foam cells
• Later followed by formation of atherosclerotic plaques (Nicholson et al., 2006)
• CD36 binds oxidized LDL with higher affinity than any other currently known scavenger receptor
• Binding of CD36 ectodomain with several molecules of fatty acids (FA)
• Binds various structural forms of long-chain FA
• Binding is dose-dependent
• High affinity of FA to CD36 on several or all sites
• Can likely affect the protein conformation
• Influence oxidized LDL uptake by increasing the FA levels
• Then enhances the uptake of oxidized LDL (Jay et al., 2015)

CD36 gene

• Located on human chromosome 7,
• Band q11.2
• Consists of 15 exons
• Exons 1, 2 and 15 are non-coding
• At least 32kb long
• Exon 3 encode N-terminal domain
• Exon 14 encodes C-terminal domain of CD36
• Major transcription initiation site located at position +290
• ATG condon on the first exon at position +62 had been found [1]

Inhibice

Expression almost completely inhibited

• During the differentiation of
• Erythrocytes [1]

Stimulace

• Activation of expression enhanced
• Mostly during the differentiation
• Of platelets
• Adipocytes
• Macrophages from their precursors [1]

Zařazení a popis struktury

• One polypeptide chain with various lengths
• From 78 to 88 kDa
• Based on the cell type
• Transmembrane glycoprotein
• Class B scavenger receptor family
• On the cell surface
• Two transmembrane domains
• Two cytoplasmic tails at both terminal ends
• One highly glycosylated extracellular domain [1]

The extracellular domain

• Encoded by 11 exons
• Consequence of various interactions
• Can be modified by glycosylation
• Necessary for
• The folding
• Transportation of protein to the cell surface
• Not necessary for ligand recognition (Armesilla and Vega, 1994; Hoosdally et al., 2009).
• Non-glycosylatable CD36
• Unable to reach the surface [1]

Synonyma

• Platelet glycoprotein
• Leukocyte differentiation antigen CD36
• Fatty acid translocase (FAT)
• Thrombospondin (TSP) receptor [1]