A novel sulfur dioxide probe inhibits high glucose-induced endothelial cell senescence

Hui Ren; WenWen Han; Shuo Wang; BaoXiang Zhao; JunYing Miao; ZhaoMin Lin

doi:10.3389/fphys.2022.979986

A novel sulfur dioxide probe inhibits high glucose-induced endothelial cell senescence

Front Physiol. 2022 Dec 16:13:979986. doi: 10.3389/fphys.2022.979986. eCollection 2022.

Authors

Hui Ren¹, WenWen Han¹, Shuo Wang¹, BaoXiang Zhao², JunYing Miao¹, ZhaoMin Lin³

Affiliations

¹ Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, China.
² Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.
³ Institute of Medical Science, The Second Hospital of Shandong University, Jinan, China.

Abstract

Sulfur dioxide (SO₂) is an important gas signal molecule produced in the cardiovascular system, so it has an important regulatory effect on human umbilical vascular endothelial cells (HUVECs). Studies have shown that high glucose (HG) has become the main cause of endothelial dysfunction and aging. However, the mechanism by which SO₂ regulates the senescence of vascular endothelial cells induced by HG has not yet been clarified, so it is necessary to find effective tools to elucidate the effect of SO₂ on senescence of HUVECs. In this paper, we identified a novel sulfur dioxide probe (2-(4-(dimethylamino)styryl)-1,1,3-trimethyl-1H-benzo [e]indol-3-ium, DLC) that inhibited the senescence of HUVECs. Our results suggested that DLC facilitated lipid droplets (LDs) translocation to lysosomes and triggered upregulation of LAMP1 protein levels by targeting LDs. Further study elucidated that DLC inhibited HG-induced HUVECs senescence by promoting the decomposition of LDs and protecting the proton channel of V-ATPase on lysosomes. In conclusion, our study revealed the regulatory effect of lipid droplet-targeted sulfur dioxide probes DLC on HG-induced HUVECs senescence. At the same time, it provided the new experimental evidence for elucidating the regulatory mechanism of intracellular gas signaling molecule sulfur dioxide on vascular endothelial fate.

Keywords: LAMP1; high glucose; lipid droplets; lysosomes; sulfur dioxide; vascular endothelial cell senescence.