PMID- 37845743
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240205
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 291
IP  - 2
DP  - 2024 Jan
TI  - Elevated glycosylation of CD36 in platelets is a risk factor for oxLDL-mediated 
      platelet activation in type 2 diabetes.
PG  - 376-391
LID - 10.1111/febs.16976 [doi]
AB  - Platelet activation and related cardiovascular complications are the hallmarks of 
      type 2 diabetes (T2D). We investigated the mechanism of platelet activation in 
      T2D using MS-based identification of differentially expressed platelet proteins 
      with a focus on glycosylated forms. Glycosylation is considered one of the common 
      post-translational modifications in T2D, and N/O-linked glycosylation of 
      glycoproteins (GPs)/integrins is known to play crucial roles in platelet 
      activation. Our platelet proteome data revealed elevated levels of GPs GPIbalpha, 
      GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had 
      elevated N-linked glycosylation of CD36 at asparagine (Asn)(408,417) . Enrichment 
      analysis revealed a close association of glycosylated CD36 with thrombospondin-1, 
      fibrinogen and SERPINA1 in T2D platelets. The glycosylation of CD36 has 
      previously been reported to increase cellular uptake of long-chain fatty acids. 
      Our in silico molecular docking data also showed a favorable binding of 
      cholesterol with glycosylated Asn(417) CD36 compared to the non-glycosylated 
      form. We further investigated the CD36:LDL cholesterol axis in T2D. Elevated 
      levels of oxidized-low density lipoprotein (oxLDL) were found to cause 
      significant platelet activation via CD36-mediated stimulation of Lyn-JNK 
      signaling. Sulfo-N-succinimidyl oleate, an inhibitor of CD36, effectively 
      inhibited oxLDL-mediated platelet activation and adhesion in vitro. Our study 
      suggests increased glycosylation of CD36 in T2D platelets as a potential route 
      for oxLDL-mediated platelet activation. The oxLDL:CD36 axis may thus be exploited 
      as a prospective target to develop therapeutics against thrombosis in T2D.
CI  - (c) 2023 Federation of European Biochemical Societies.
FAU - Agarwal, Sakshi
AU  - Agarwal S
AD  - Regional Centre for Biotechnology, National Capital Region Biotech Science 
      Cluster, Faridabad, India.
FAU - Saha, Sandhini
AU  - Saha S
AD  - Regional Centre for Biotechnology, National Capital Region Biotech Science 
      Cluster, Faridabad, India.
FAU - Ghosh, Riya
AU  - Ghosh R
AD  - Regional Centre for Biotechnology, National Capital Region Biotech Science 
      Cluster, Faridabad, India.
FAU - Sarmadhikari, Debapriyo
AU  - Sarmadhikari D
AD  - Translational Health Science Technology Institute, National Capital Region 
      Biotech Science Cluster, Faridabad, India.
FAU - Asthana, Shailendra
AU  - Asthana S
AUID- ORCID: 0000-0002-6143-7500
AD  - Translational Health Science Technology Institute, National Capital Region 
      Biotech Science Cluster, Faridabad, India.
FAU - Maiti, Tushar K
AU  - Maiti TK
AD  - Regional Centre for Biotechnology, National Capital Region Biotech Science 
      Cluster, Faridabad, India.
FAU - Khadgawat, Rajesh
AU  - Khadgawat R
AD  - All India Institute of Medical Sciences, New Delhi, India.
FAU - Guchhait, Prasenjit
AU  - Guchhait P
AUID- ORCID: 0000-0002-6601-6692
AD  - Regional Centre for Biotechnology, National Capital Region Biotech Science 
      Cluster, Faridabad, India.
LA  - eng
GR  - BT/PR22881/Department of Biotechnology, Ministry of Science and Technology, 
      India/
GR  - BT/PR22985/Department of Biotechnology, Ministry of Science and Technology, 
      India/
GR  - CRG/000092/Science and Engineering Research Board/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231027
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (oxidized low density lipoprotein)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Integrins)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Glycosylation
MH  - Molecular Docking Simulation
MH  - Platelet Activation/physiology
MH  - Lipoproteins, LDL/pharmacology
MH  - Risk Factors
MH  - Integrins/metabolism
OTO - NOTNLM
OT  - CD36
OT  - T2D patients
OT  - glycosylation
OT  - oxLDL
OT  - platelet glycoproteins
EDAT- 2023/10/17 00:42
MHDA- 2024/01/22 06:43
CRDT- 2023/10/16 23:56
PHST- 2023/08/19 00:00 [revised]
PHST- 2023/06/27 00:00 [received]
PHST- 2023/10/12 00:00 [accepted]
PHST- 2024/01/22 06:43 [medline]
PHST- 2023/10/17 00:42 [pubmed]
PHST- 2023/10/16 23:56 [entrez]
AID - 10.1111/febs.16976 [doi]
PST - ppublish
SO  - FEBS J. 2024 Jan;291(2):376-391. doi: 10.1111/febs.16976. Epub 2023 Oct 27.