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Upregulation of the secretory pathway Ca 2+ /Mn 2+ -ATPase isoform 1 in LPS-stimulated microglia and its involvement in Mn 2+ -induced Golgi fragmentation.
- Source :
-
Glia [Glia] 2024 Jun; Vol. 72 (6), pp. 1201-1214. Date of Electronic Publication: 2024 Mar 14. - Publication Year :
- 2024
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Abstract
- 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. Ca <superscript>2+</superscript> signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca <superscript>2+</superscript> store, which involves the Ca <superscript>2+</superscript> transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca <superscript>2+</superscript> store that depends on the secretory pathway Ca <superscript>2+</superscript> /Mn <superscript>2+</superscript> -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 Mn <superscript>2+</superscript> transporter and considering that Mn <superscript>2+</superscript> excess causes manganism in the brain, we addressed the role of microglial SPCA1 in Mn <superscript>2+</superscript> toxicity. Our results revealed a clear effect of Mn <superscript>2+</superscript> 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 Mn <superscript>2+</superscript> by washing improved the culture viability, although it did not effectively reverse Golgi fragmentation. Interestingly, pretreatment with curcumin maintained microglia cultures viable, prevented Mn <superscript>2+</superscript> -induced Golgi fragmentation, and preserved SPCA Ca <superscript>2+</superscript> -dependent activity, suggesting curcumin as a potential protective agent against Mn <superscript>2+</superscript> -induced Golgi alterations in microglia.<br /> (© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)
- Subjects :
- Lipopolysaccharides toxicity
Microglia metabolism
Calcium-Transporting ATPases genetics
Calcium-Transporting ATPases metabolism
Secretory Pathway
Up-Regulation
Golgi Apparatus metabolism
Golgi Apparatus ultrastructure
Membrane Transport Proteins metabolism
Protein Isoforms metabolism
Calcium metabolism
Adenosine Triphosphatases metabolism
Curcumin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1136
- Volume :
- 72
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Glia
- Publication Type :
- Academic Journal
- Accession number :
- 38482950
- Full Text :
- https://doi.org/10.1002/glia.24528