The eyes are exposed to constant irradiation, and therefore have extraordinary need for antioxidant protection 1. In addition, we found that autophagy is activated in the process of ferroptosis and reduces SIPS, suggesting an essential role of autophagy in ferroptosis and SIPS. Our findings suggest that GSH depletion induces ferroptosis, autophagy, and SIPS. In contrast, inducing autophagy with rapamycin (100вЂ‰nM) attenuated SIPS. Inhibiting autophagy with Baf-A1 (75вЂ‰nM) or 3-MA (10вЂ‰mM) promoted SIPS. GSH depletion-dependent cell death was prevented by selective ferroptosis inhibitors (8вЂ‰ОјM Fer-1 and 600вЂ‰nM Lip-1), iron chelator DFO (80вЂ‰ОјM), as well as autophagic inhibitors Baf-A1 (75вЂ‰nM) and 3-MA (10вЂ‰mM). In addition, GSH depletion induced SIPS, as evidenced by increased percentage of the senescence-associated ОІ-galactosidase-positive cells, increased senescence-associated heterochromatin foci (SAHF), as well as cell cycle arrest at the G1 phase. Increased autophagy was apparent, as reflected by increased LC3 expression, autophagic vacuoles, and autophagic flux. Western blot analysis revealed decreased expression of ferroptotic modulator glutathione peroxidase 4 (GPX4). These treatments decreased cell viability and increased both soluble and lipid reactive oxygen species (ROS) generation but did not affect mitochondrial ROS or mitochondrial mass. Briefly, cultured ARPE-19 cells were depleted of GSH using: (1) incubation in cystine (Cys 2)-free culture medium (2) treatment with buthionine sulphoximine (BSO, 1000вЂ‰ВµM) to block de novo GSH synthesis for 24вЂ“48вЂ‰h or (3) treatment with erastin (10вЂ‰ВµM for 12вЂ“24вЂ‰h) to inhibit Cys 2/glutamate antiporter (system x c в€’). We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells. Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). The findings of this study provide structural insights into the mechanism of the immune escape of P.В falciparum and the endless arms race between parasite and host.Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). We then verify that RIFIN could induce LAIR1-mediated cell signaling, and LAIR1-containing antibodies could block the pathway. Surprisingly, RIFINs use completely different binding sites to bind to LAIR1 or LILRB1, indicating the kaleidoscopic change of RIFINs. Notably, the two RIFINs engage similar binding sites on LAIR1 with different angles, and the RIFIN-binding sites overlap with the collagen-binding site. In this study, we solve a LAIR1-binding RIFIN structure: the complex structures of two RIFINs bound to mutated or wild-type LAIR1 in two distinct patterns. Public antibodies with LAIR1 insertion have been identified from malarial patients against a subset of RIFINs. P.В falciparum expresses variable erythrocyte surface antigens such as RIFINs. Malaria infection by Plasmodium falciparum continues to pose a global threat to the human population.

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