2. Academic Validation
  3. Identification of a new autophagy inhibitor targeting lipid droplets in vascular endothelial cells

Identification of a new autophagy inhibitor targeting lipid droplets in vascular endothelial cells

  • Biochem Biophys Res Commun. 2021 Sep 24:571:195-200. doi: 10.1016/j.bbrc.2021.07.078.
Hui Ren 1,  Wen Yao 1,  Qun Wei 2,  Jun Zhang 1,  BaoXiang Zhao 3,  JunYing Miao 4
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, PR China.
  • 2 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, PR China; Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, 250012, Shandong, PR China.
  • 3 Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, PR China.
  • 4 Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao, 266237, PR China. Electronic address: [email protected].
PMID: 34330064 DOI: 10.1016/j.bbrc.2021.07.078
Abstract

Autophagy of vascular endothelial cells (VECs) plays an important role in maintaining vascular homeostasis. Lipid droplets (LDs) are organelles that can be formed in response to various stimuli, including excessive lipid or various stresses. LDs sequester toxic lipids, thereby preventing lipotoxic cell damage and have a complex relationship with Autophagy. In the previous study, we identified a novel Grp94 inhibitor HCP1 inhibited Apoptosis in VECs. Here we found that HCP1 targeted LDs and promoted the accumulation of LDs in VECs. Our results showed that HCP1 upregulated the protein levels of autophagy-related proteins. We demonstrated that HCP1 upregulated the number of LDs and suppressed Autophagy by inhibiting Grp94. Therefore, we provided HCP1 as a new VECs Autophagy inhibitor targeting LDs, which might be a potential compound in the treatment of VECs Autophagy related vascular diseases.

Keywords

Autophagy; Grp94; Lipid droplets; Vascular endothelial cells.

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