Arrestin domain-containing protein 1-mediated microvesicles (ARMMs) protect against cadmium-induced neurotoxicity

• DOI: 10.1016/j.vesic.2023.100027
• Publication Date: 2023-07-14T17:18:01Z
• Authors: Zunwei Chen; Zhi Qiao; Charlotte R. Wirth; Hae-Ryung Park; Quan Lu
• Keywords: Neurotoxicity

Exposure to environmental heavy metals such as cadmium (Cd) is often linked neurotoxicity but the underlying mechanisms remain poorly understood. Here we show that Arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs)–an important class of extracellular vesicles (EVs) whose biogenesis occurs at plasma membrane–protect against Cd-induced neurotoxicity. Cd increased production EVs, including ARMMs, in a human neural progenitor cell line, ReNcell CX (ReN) cells. ReN cells lack ARMMs result CRISPR-mediated ARRDC1 knockout were more susceptible toxicity evidenced by LDH well elevated level oxidative stress markers. Importantly, adding back ARRDC1-knockout significantly reduced toxicity. Consistent with this finding, proteomics data showed anti-oxidative proteins are enriched secreted from Together our study reveals novel protective role and suggests may be used therapeutically reduce caused exposure potentially other metal toxicants.