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Nanoplastics (NPs) pollution poses a huge threat to the ecosystem and has become one of the environmental pollutants that have attracted much attention. There is increasing evidence that both oxidative stress and endoplasmic reticulum stress (ERS) are associated with polystyrene nanoplastics (PS‐NPs) exposure. Lipopolysaccharide (LPS) has been shown to induce apoptotic damage in various tissues, but whether PS‐NPs can aggravate LPS‐induced apoptosis in mouse kidneys through oxidative stress‐regulated inositol‐requiring enzyme 1 (IRE1)/X‐box binding protein 1 (XBP1) ERS pathway remains unclear. In this study, based on the establishment of in vitro and in vivo PS‐NPs and LPS exposure models alone and in combination in mice and HEK293 cells, the effects and mechanisms of PS‐NPs on LPS‐induced renal cell apoptosis were investigated. The results showed that PS‐NPs could aggravate LPS‐ induced apoptosis. PS‐NPs/LPS can induce ERS through oxidative stress, activate the IRE1/XBP1 pathway, and promote the expression of apoptosis markers (Caspase‐3 and Caspase‐12). Kidney oxidative stress, ERS, and apoptosis in PS‐ NPs + LPS combined exposure group were more severe than those in the single exposure group. Interestingly, 4‐phenylbutyric acid‐treated HEK293 cells inhibited the expression of the IRE1/XBP1 ERS pathway and apoptotic factors in the PS‐NPs + LPS combined exposure group. N‐acetyl‐L‐cysteine effectively blocked the activation of the IRE1/XBP1 ERS pathway, suggesting that PS‐NPs‐ induced oxidative stress is an early event that triggers ERS. Collectively, these results confirmed that PS‐NPs aggravated LPS‐induced apoptosis through the oxidative stress‐induced IRE1/XBP1 ERS pathway. Our study provides new insights into the health threats of PS‐NPs exposed to mammals and humans. [ABSTRACT FROM AUTHOR]

The Drosophila lymph gland houses blood progenitors that give rise to myeloid-like blood cells. Initially, blood progenitors proliferate, but later, they become quiescent to maintain multipotency before differentiation. Despite the identification of various factors involved in multipotency maintenance, the cellular mechanism controlling blood progenitor quiescence remains elusive. Here, we identify the expression of nitric oxide synthase in blood progenitors, generating nitric oxide for post-translational S-nitrosylation of protein cysteine residues. S-nitrosylation activates the Ire1-Xbp1-mediated unfolded protein response, leading to G2 cell-cycle arrest. Specifically, we identify the epidermal growth factor receptor as a target of S-nitrosylation, resulting in its retention within the endoplasmic reticulum and blockade of its receptor function. Overall, our findings highlight developmentally programmed S-nitrosylation as a critical mechanism that induces protein quality control in blood progenitors, maintaining their undifferentiated state by inhibiting cell-cycle progression and rendering them unresponsive to paracrine factors. [Display omitted] • Nitric oxide (NO) is produced in blood progenitors of the Drosophila lymph gland • This NO is utilized for the S-nitrosylation of target proteins, including EGFR • The S-nitrosylation of EGFR attenuates its membrane trafficking in blood progenitors • S-nitrosylation activates the UPR pathway to arrest progenitors in the G2 cell cycle Cho et al. demonstrated that NO facilitates S-nitrosylation in blood progenitors, which triggers the UPR to pause the progenitor cell cycle in the G2 phase. Notably, they identified EGFR as a target of S-nitrosylation, which alters its membrane trafficking, allowing progenitor cells to timely activate the EGFR pathway for differentiation. [ABSTRACT FROM AUTHOR]

Regeneration of skeletal muscle in adults is mediated by satellite stem cells. Accumulation of misfolded proteins triggers endoplasmic reticulum stress that leads to unfolded protein response (UPR). The UPR is relayed to the cell through the activation of PERK, IRE1/XBP1, and ATF6. Here, we demonstrate that levels of PERK and IRE1 are increased in satellite cells upon muscle injury. Inhibition of PERK, but not the IRE1 arm of the UPR in satellite cells inhibits myofiber regeneration in adult mice. PERK is essential for the survival and differentiation of activated satellite cells into the myogenic lineage. Deletion of PERK causes hyper-activation of p38 MAPK during myogenesis. Blocking p38 MAPK activity improves the survival and differentiation of PERK-deficient satellite cells in vitro and muscle formation in vivo. Collectively, our results suggest that the PERK arm of the UPR plays a pivotal role in the regulation of satellite cell homeostasis during regenerative myogenesis.