[Gly14]-humanin restores cathepsin D function via FPRL1 and promotes autophagic degradation of Ox-LDL in HUVECs.
Ding. Yu Y; Feng. Yue Y; Zou. Yutian Y; Wang. Fen F; Liu. Huihui H; Liu. Chunfeng C; Zhang. Yanlin Y
Key Findings
- Ox‑LDL causes lipid buildup and impairs cathepsin D activity in endothelial cells.
- HNG reduces lipid/cholesterol accumulation, restores cathepsin D function, and normalizes autophagy markers (↑LC3‑II, ↓P62).
- Blocking the FPRL1 receptor eliminates HNG’s protective effects, confirming the pathway.
Practical Outcomes
- This is early‑stage cell research, so it isn’t ready for direct supplementation. It suggests humanin analogs could one day support vascular health and atherosclerosis prevention, but human dosing, safety, and efficacy are still unknown. Biohackers should wait for animal or clinical data before considering use.
Summary
A modified humanin peptide (HNG) helps blood vessel cells clear harmful oxidized LDL by fixing a lysosomal enzyme (cathepsin D) through the FPRL1 receptor, which improves the cell's waste‑removal system and reduces lipid buildup.
Abstract
Abnormal aggregation of oxidized low-density lipoprotein (Ox-LDL) in vascular endothelial cells (VECs) is one of the major pathological changes in atherosclerotic lesions. Our research aimed to assess the mechanism of humanin (HN) in promoting autophagic degradation of Ox-LDL in HUVECs. Flow cytometry and lipid quantitation results showed that Ox-LDL caused lipid and cholesterol accumulation in HUVECs. Western blot results showed that Ox-LDL increased the expression of autophagy-related proteins P62 and LC3-II in a concentration-dependent manner. The cathepsin D activity assay showed that Ox-LDL inhibited the function of cathepsin D. HNG pretreatment reduced lipid and cholesterol aggregation in HUVECs induced by Ox-LDL, increased LC3-II protein level, decreased P62 protein content, and reversed Ox-LDL-induced cathepsin D functional impairment. Inhibition of the FPRL1 pathway by FPRL1 siRNA or the FPRL1-specific inhibitor Boc-MLF blocked all HNG's protective effects. These results indicate that HNG could restore cathepsin D activity and protein level in HUVECs to repair lysosomal functional damage induced by Ox-LDL, further repairing Ox-LDL-induced autophagic damage in HUVECs. HNG restores the activity of Ox-LDL-induced damaged lysosomal enzyme cathepsin D through its membrane protein receptor FPRL1 to promote autophagic degradation of Ox-LDL in HUVECs.
Study Information
pubmed
2020
2020-07-25T00:00:00.000Z
10.1016/j.numecd.2020.07.022
10
41