Upregulation of the secretory pathway Ca2+/Mn2+-ATPase isoform 1 in LPS-stimulated microglia and its involvement in Mn2+-induced Golgi fragmentation Bhojwani-Cabrera, AM Bautista-García, A. Neubrand, Veronika Elisabeth Membrive-Jiménez, F. A. Bramini, Mattia Martín Oliva, Francisco David Cuadros Ojeda, Miguel Ángel Marín Teva, José Luis Navascues Martínez, Julio Vangheluwe, Peter Sepúlveda Justo, María Del Rosario Golgi Brain Calcium This is the peer reviewed version of the following article: Bhojwani-Cabrera AM, Bautista-García A, Neubrand VE, Membrive-Jiménez FA, Bramini M, Martin-Oliva D, Cuadros MA, Marín-Teva JL, Navascués J, Vangheluwe P, Sepúlveda MR. Upregulation of the secretory pathway Ca2+ /Mn2+ -ATPase isoform 1 in LPS-stimulated microglia and its involvement in Mn2+ -induced Golgi fragmentation. Glia. 2024 Mar 14, which has been published in final form at https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24528. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Microglia play an important protective role in the healthy nervous tissue, being able to react to a variety of stimuli that induce different intracellular cascades for specific tasks. Ca2+ signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca2+ store, which involves the Ca2+ transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca2+ store that depends on the secretory pathway Ca2+ /Mn2+ -transport ATPase isoform 1 (SPCA1). We found upregulation of SPCA1 upon lipopolysaccharide stimulation of microglia BV2 cells and primary microglia, where alterations of the Golgi ribbon were also observed. Silencing and overexpression experiments revealed that SPCA1 affects cell morphology, Golgi apparatus integrity, and phagocytic functions. Since SPCA1 is also an efficient Mn2+ transporter and considering that Mn2+ excess causes manganism in the brain, we addressed the role of microglial SPCA1 in Mn2+ toxicity. Our results revealed a clear effect of Mn2+ excess on the viability and morphology of microglia. Subcellular analysis showed Golgi fragmentation and subsequent alteration of SPCA1 distribution from early stages of toxicity. Removal of Mn2+ by washing improved the culture viability, although it did not effectively reverse Golgi fragmentation. Interestingly, pretreatment with curcumin maintained microglia cultures viable, prevented Mn2+ -induced Golgi fragmentation, and preserved SPCA Ca2+ -dependent activity, suggesting curcumin as a potential protective agent against Mn2+ -induced Golgi alterations in microglia. 2024-04-01T07:47:49Z 2024-04-01T07:47:49Z 2024 info:eu-repo/semantics/article Glia: 1–14 https://hdl.handle.net/10481/90240 10.1002/glia.24528 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Wiley