Hormetic Effects of 7‐Ketocholesterol in Preventing Ferroptosis in Hepatocytes
Sarit Anavi, Nicole Giltman, Haim Zeigerman, Zecharia Madar, Oren Tirosh
TL;DR
Low levels of 7-ketocholesterol protect liver and nerve cells from a type of cell death called ferroptosis, but high levels are harmful.
Contribution
The study reveals that low concentrations of 7KC have hormetic effects in preventing ferroptosis in hepatocytes and neurons.
Findings
Low concentrations of 7KC reduced ferroptosis in hepatocytes and neurons by lowering lipid peroxidation and MDA levels.
7KC suppressed cholesterol synthesis and lipid accumulation, contrasting with the effects of Erastin.
7KC showed stronger anti-ferroptotic effects than 7DHC, possibly via upregulation of GCLC.
Abstract
Ferroptosis, a form of cell death marked by iron dysregulation and lipid peroxidation, has been implicated in liver and neurodegenerative diseases. 7‐ketocholesterol (7KC), a cholesterol oxidation product, induces oxidative stress and inflammation at high concentrations. However, the effects of low, subtoxic levels of 7KC are unclear. This study investigates the potential hormetic effects of low concentrations of 7KC on hepatocytes and neuronal cells during ferroptosis. Ferroptosis was induced in AML12 hepatocytes using 20 µM Erastin, with cells co‐treated with varying concentrations of 7KC. Cell death was assessed, and gene expression was analyzed via RNA sequencing (RNA‐seq) and real‐time PCR. HT4 hippocampal neuronal cells were treated with glutamate to induce ferroptosis, both with and without 7KC. Low, nontoxic concentrations of 7KC protected both hepatocytes and neuronal cells…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Figure 25
Figure 26
Figure 27Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsFerroptosis and cancer prognosis · Cholesterol and Lipid Metabolism · Cancer, Lipids, and Metabolism