Transaldolase inhibits CD36 expression by modulating glutathione-p38 signaling, exerting protective effects against macrophage foam cell formation.

Abstract

In atherosclerosis, macrophage-derived foam cell formation is considered to be a hallmark of the pathological process; this occurs via the uptake of modified lipoproteins. In the present study, we aim to determine the role of transaldolase in foam cell formation and atherogenesis and reveal the mechanisms underlying its role. Bone marrow-derived macrophages (BMDMs) isolated from mice successfully form foam cells after treatment with oxidized low-density lipoprotein (80 μg/mL). Elevated transaldolase levels in the foam cell model are assessed by quantitative polymerase chain reaction and western blot analysis. Transaldolase overexpression and knockdown in BMDMs are achieved via plasmid transfection and small interfering RNA technology, respectively. We find that transaldolase overexpression effectively attenuates, whereas transaldolase knockdown accelerates, macrophage-derived foam cell formation through the inhibition or activation of cholesterol uptake mediated by the scavenger receptor cluster of differentiation 36 (CD36) in a p38 mitogen-activated protein kinase (MAPK) signaling-dependent manner. Transaldolase-mediated glutathione (GSH) homeostasis is identified as the upstream regulator of p38 MAPK-mediated CD36-dependent cholesterol uptake in BMDMs. Transaldolase upregulates GSH production, thereby suppressing p38 activity and reducing the CD36 level, ultimately preventing foam cell formation and atherosclerosis. Thus, our findings indicate that the transaldolase-GSH-p38-CD36 axis may represent a promising therapeutic target for atherosclerosis.

• Authors: Chengyi Li, Zihao Song, Pengyue Gao, Wei Duan, Xiu Liu, Sijia Liang, Quan Gong, Jiawei Guo
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 55 Issue 9 Pg. 1496-1505 (Aug 01 2023) ISSN: 1745-7270 [Electronic] China
• PMID: 37528662 (Publication Type: Journal Article)

Chemical References

• Transaldolase
• CD36 Antigens
• Lipoproteins, LDL
• Glutathione
• p38 Mitogen-Activated Protein Kinases
• Cholesterol

Topics

• Mice
• Animals
• Foam Cells
• Transaldolase (metabolism, pharmacology)
• CD36 Antigens (genetics, metabolism)
• Macrophages (metabolism)
• Lipoproteins, LDL (metabolism)
• Atherosclerosis (metabolism)
• Glutathione (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)
• Cholesterol (metabolism)