General Information of the Ferroptosis Regulator (ID: REG10385)
Regulator Name Platelet glycoprotein 4 (CD36)
Synonyms
GP3B; GP4; Fatty acid translocase; Glycoprotein IIIb; Leukocyte differentiation antigen CD36; PAS IV; PAS-4; Platelet collagen receptor; Platelet glycoprotein IV; Thrombospondin receptor; CD_antigen=CD36
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Gene Name CD36
Gene ID 948
Regulator Type Protein coding
Uniprot ID P16671
Sequence
MGCDRNCGLIAGAVIGAVLAVFGGILMPVGDLLIQKTIKKQVVLEEGTIAFKNWVKTGTE
VYRQFWIFDVQNPQEVMMNSSNIQVKQRGPYTYRVRFLAKENVTQDAEDNTVSFLQPNGA
IFEPSLSVGTEADNFTVLNLAVAAASHIYQNQFVQMILNSLINKSKSSMFQVRTLRELLW
GYRDPFLSLVPYPVTTTVGLFYPYNNTADGVYKVFNGKDNISKVAIIDTYKGKRNLSYWE
SHCDMINGTDAASFPPFVEKSQVLQFFSSDICRSIYAVFESDVNLKGIPVYRFVLPSKAF
ASPVENPDNYCFCTEKIISKNCTSYGVLDISKCKEGRPVYISLPHFLYASPDVSEPIDGL
NPNEEEHRTYLDIEPITGFTLQFAKRLQVNLLVKPSEKIQVLKNLKRNYIVPILWLNETG
TIGDEKANMFRSQVTGKINLLGLIEMILLSVGVVMFVAFMISYCACRSKTIK

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Family CD36 family
Function
Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor- ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (Probable). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (By similarity). Mechanistically, binding of fatty acids activates downstream kinase LYN, which phosphorylates the palmitoyltransferase ZDHHC5 and inactivates it, resulting in the subsequent depalmitoylation of CD36 and caveolar endocytosis. In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway (By similarity). Involved in oral fat perception and preferences. Detection into the tongue of long- chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions (By similarity). In taste receptor cells, mediates the induction of an increase in intracellular calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (By similarity). Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis (By similarity). Receptor for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (By similarity). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting together with THBS1 (By similarity). As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome (By similarity). Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (By similarity). { |UniProtKB:Q07969, |UniProtKB:Q08857, | , | , | , | , | , | , | , | , | }.; (Microbial infection) Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling. { | , | , | }.

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HGNC ID
HGNC:1663
KEGG ID hsa:948
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
CD36 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Cardiomyopathy ICD-11: BC43
Responsed Drug Astragaloside IV Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Male Sprague-Dawley (SD) rats (160-180 g) were purchased from the Experimental Animal Center of Guangzhou University of Chinese Medicine. After 1 week of acclimatization, the rats were randomly divided into two groups: the control group (standard diet,n = 6) and the high-fat diet (HFD) group. The control group was given a standard diet for 8 weeks, and the HFD group was given a high-fat diet (feed item No. D12451, Guangdong Medical Laboratory Animal Center) for 8 weeks. Subsequently, intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) was performed in the HFD group for inducing diabetic symptoms, and an equal volume of saline was given to the control group. A diabetes model was successfully established under the condition that the fasting blood glucose levels were > 16.7 mmol/L over three consecutive days. Diabetic rats in the HFD group were divided into five groups: a DCM group, three AS-IV treatment groups (20, 40, and 80 mg/kg/day by gavage,n = 6), and an atorvastatin treatment group (ALE group, used as a positive control drug, 10 mg/kg, by gavage,n = 6). Rats were given the standard diet during drug gavage. After 12 weeks of treatment, all animals were anesthetized and then euthanized by intraperitoneal injection with an overdose of pentobarbital sodium. The animal experiments in this study were randomized and single-blind.

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Response regulation Astragaloside IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in diabetic cardiomyopathy rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment.
Cardiomyopathy [ICD-11: BC43]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Platelet glycoprotein 4 (CD36) Protein coding
Responsed Drug Astragaloside IV Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Male Sprague-Dawley (SD) rats (160-180 g) were purchased from the Experimental Animal Center of Guangzhou University of Chinese Medicine. After 1 week of acclimatization, the rats were randomly divided into two groups: the control group (standard diet,n = 6) and the high-fat diet (HFD) group. The control group was given a standard diet for 8 weeks, and the HFD group was given a high-fat diet (feed item No. D12451, Guangdong Medical Laboratory Animal Center) for 8 weeks. Subsequently, intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) was performed in the HFD group for inducing diabetic symptoms, and an equal volume of saline was given to the control group. A diabetes model was successfully established under the condition that the fasting blood glucose levels were > 16.7 mmol/L over three consecutive days. Diabetic rats in the HFD group were divided into five groups: a DCM group, three AS-IV treatment groups (20, 40, and 80 mg/kg/day by gavage,n = 6), and an atorvastatin treatment group (ALE group, used as a positive control drug, 10 mg/kg, by gavage,n = 6). Rats were given the standard diet during drug gavage. After 12 weeks of treatment, all animals were anesthetized and then euthanized by intraperitoneal injection with an overdose of pentobarbital sodium. The animal experiments in this study were randomized and single-blind.

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Response regulation Astragaloside IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in diabetic cardiomyopathy rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment.
Astragaloside IV [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Unspecific Target
Responsed Disease Cardiomyopathy ICD-11: BC43
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
In Vivo Model
Male Sprague-Dawley (SD) rats (160-180 g) were purchased from the Experimental Animal Center of Guangzhou University of Chinese Medicine. After 1 week of acclimatization, the rats were randomly divided into two groups: the control group (standard diet,n = 6) and the high-fat diet (HFD) group. The control group was given a standard diet for 8 weeks, and the HFD group was given a high-fat diet (feed item No. D12451, Guangdong Medical Laboratory Animal Center) for 8 weeks. Subsequently, intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) was performed in the HFD group for inducing diabetic symptoms, and an equal volume of saline was given to the control group. A diabetes model was successfully established under the condition that the fasting blood glucose levels were > 16.7 mmol/L over three consecutive days. Diabetic rats in the HFD group were divided into five groups: a DCM group, three AS-IV treatment groups (20, 40, and 80 mg/kg/day by gavage,n = 6), and an atorvastatin treatment group (ALE group, used as a positive control drug, 10 mg/kg, by gavage,n = 6). Rats were given the standard diet during drug gavage. After 12 weeks of treatment, all animals were anesthetized and then euthanized by intraperitoneal injection with an overdose of pentobarbital sodium. The animal experiments in this study were randomized and single-blind.

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Response regulation Astragaloside IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in diabetic cardiomyopathy rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment.
References
Ref 1 Astragaloside IV attenuates myocardial dysfunction in diabetic cardiomyopathy rats through downregulation of CD36-mediated ferroptosis. Phytother Res. 2023 Jul;37(7):3042-3056. doi: 10.1002/ptr.7798. Epub 2023 Mar 7.