{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNPGPx, a unique member of the glutathione peroxidase family that lacks a critical selenocysteine residue, has emerged as an important oxidative stress sensor. Under oxidative conditions, NPGPx forms an inter-cysteine disulfide bond that facilitates its binding with the ER chaperone GRP78, thereby enhancing GRP78’s ability to refold misfolded proteins and restore ER homeostasis. In cells lacking NPGPx, reactive oxygen species accumulate, leading not only to an impaired stress response but also to an ROS‐dependent promotion of adipocyte differentiation, suggesting its protective role extends to metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSimilarly, GPx7, an ER-resident glutathione peroxidase that contains a peroxidatic cysteine without the resolving cysteine typical of related enzymes, plays a key role in maintaining redox balance. Biochemically distinct, GPx7 participates in diverse cellular processes. In mesenchymal stem cells, for instance, GPx7 deficiency has been shown to inhibit osteogenesis while promoting adipogenesis by triggering ER stress and downregulating the mTOR signaling pathway. In parallel, in the context of hepatic stress, GPx7 exhibits an anti-fibrotic effect by curtailing ROS production and suppressing pro-inflammatory and pro-fibrotic gene expression, thereby alleviating the progression of non-alcoholic steatohepatitis-associated fibrosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pei-Chi Wei, Yi-Hsuan Hsieh, Mei-I Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of the oxidative stress sensor NPGPx compromises GRP78 chaperone activity and induces systemic disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2012.10.007"}], "href": "https://doi.org/10.1016/j.molcel.2012.10.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23123197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23123197"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yi-Cheng Chang, Yu-Hsiang Yu, Jin-Yuh Shew, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Mol Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/emmm.201302679"}], "href": "https://doi.org/10.1002/emmm.201302679"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23828861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23828861"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Valentina Bosello-Travain, Marcus Conrad, Giorgio Cozza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein disulfide isomerase and glutathione are alternative substrates in the one Cys catalytic cycle of glutathione peroxidase 7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2013.02.017"}], "href": "https://doi.org/10.1016/j.bbagen.2013.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23454490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23454490"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hyeon Ju Kim, Yoseob Lee, Sungsoon Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPx7 ameliorates non-alcoholic steatohepatitis by regulating oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMB Rep (2020)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32317079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32317079"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xuchen Hu, Boer Li, Fanzi Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPX7 Facilitates BMSCs Osteoblastogenesis via ER Stress and mTOR Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.16974"}], "href": "https://doi.org/10.1111/jcmm.16974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34626080"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34626080"}]}]}]}