Rheumatology: Glycine changes in iron concentration in rheumatoid arthritis through SAM-mediated methylation of GPX4 promoter

Rheumatoid arthritis (RA) is a chronic autoimmune disease that destroys joint bone and cartilage
.

Its pathological feature is synovial hyperplasia, which gradually promotes the formation of vascular pans to damage cartilage

Although different cell death modes have been explored, recent studies have generally focused on FLS apoptosis in RA
.

A recent study showed that oxidative stress-induced phospholipase A (PLA), which is required for the formation of oxidized lysophospholipids, promotes K/BxN serum-induced arthritis

Recent studies have reported that the antioxidant enzyme glutathione peroxidase 4 (Gpx4), induced by the XC-dependent intracellular glutathione (GSH) system, converts phospholipid peroxides into nontoxic Fatty alcohols, thereby inhibiting iron loss
.

In addition, ferritin (Ferritin, Fer) stores iron and can be degraded by the proteasome or NCOA4-mediated lysosomal pathway to release iron

Thus, both ferritin degradation and Gpx4 inactivation can promote DNA methylation, the most common epigenetic modification induced by the DNA methyltransferase family (DNMT)
.

Glycine and one-carbon metabolism are known to regulate DNA methylation

Synovial hyperplasia is a key event in aggressive vascular membrane formation and cartilage damage during rheumatoid arthritis (RA) disease progression
.

At the same time, decreased iron concentrations may play a key role in maintaining the balance of synovial proliferation and death

Synovial hyperplasia is a key event in aggressive vascular membrane formation and cartilage damage during rheumatoid arthritis (RA) disease progression

Reduced ferroptosis, acyl-CoA synthase long chain 4 (ACSL4), ferritin heavy chain 1 (FTH1), Gpx4 and cystine/glutamate in RA synovium and FLS compared to healthy controls (HC) Antiporter solute carrier family 7 member 11 (SLC7A11) increased
.

Although both lipid oxidation and antioxidant levels were higher in the RA FLS group than in the HC group, the increase in antioxidant levels was slightly higher than in the HC group

In conclusion, we demonstrated a reduction in the decline of iron concentrations in patients with rheumatoid arthritis and explored the process of glycine through SAM-mediated reduction of Gpx4 promoter methylation and ferritin

Source: Ling H, Li M, Yang C, Glycine increased ferroptosis via SAM-mediated GPX4 promoter methylation in rheumatoid arthritis.

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