{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T19:52:10Z","timestamp":1769629930589,"version":"3.49.0"},"reference-count":62,"publisher":"S. Karger AG","issue":"9-10","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Blood Purif"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Uremic retention solutes have been alleged to induce the apoptotic program of different cell types, including peripheral blood mononuclear leukocytes (PBL), which may contribute to uremic leukopenia and immune dysfunction. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; The molecular effects of these solutes were investigated in uremic PBL (u-PBL) and mononuclear cell lines (THP-1 and K562) exposed to the high molecular weight fraction of uremic plasma (u-HMW) prepared by in vitro ultrafiltration with 50 kDa cut-off microconcentrators. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; u-PBL show reduced cell viability and increased apoptotic death compared to healthy control PBL (c-PBL). u-HMW induce apoptosis both in u-PBL and c-PBL, as well as in mononuclear cell lines, also stimulating cellular H&lt;sub&gt;2&lt;\/sub&gt;O&lt;sub&gt;2&lt;\/sub&gt; formation and secretion, IRE1-\u03b1-mediated endoplasmic reticulum stress signaling, and JNK\/&lt;i&gt;c&lt;\/i&gt;Jun pathway activation. Also, u-HMW induce autophagy in THP-1 monocytes. u-PBL were characterized by the presence in their cellular proteome of the main proteins and carbonylation targets of u-HMW, namely albumin, transferrin, and fibrinogen, and by the increased expression of receptor for advanced glycation end-products, a scavenger receptor with promiscuous ligand binding properties involved in leukocyte activation and endocytosis. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; Large uremic solutes induce abnormal endocytosis and terminal alteration of cellular proteostasis mechanisms in PBL, including UPR\/ER stress response and autophagy, ultimately activating the JNK-mediated apoptotic signaling of these cells. These findings describe the suicidal role of immune cells in facing systemic proteostasis alterations of kidney disease patients, a process that we define as the immuno-proteostasis response of uremia. <\/jats:p>","DOI":"10.1159\/000533309","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:09:13Z","timestamp":1697058553000},"page":"737-750","source":"Crossref","is-referenced-by-count":6,"title":["Induction of Vesicular Trafficking and JNK-Mediated Apoptotic Signaling in Mononuclear Leukocytes Marks the Immuno-Proteostasis Response to Uremic Proteins"],"prefix":"10.1159","volume":"52","author":[{"given":"Desir\u00e9e","family":"Bartolini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria 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