Upregulation of the secretory pathway Ca2+/Mn2+ATPase isoform 1 in LPS‐stimulated microglia and its involvement in Mn2+‐induced Golgi fragmentation

Author:

Bhojwani‐Cabrera Aysha M.1ORCID,Bautista‐García Alicia1ORCID,Neubrand Veronika E.1ORCID,Membrive‐Jiménez Francisco A.1ORCID,Bramini Mattia1ORCID,Martin‐Oliva David1ORCID,Cuadros Miguel A.1ORCID,Marín‐Teva José Luis1ORCID,Navascués Julio1ORCID,Vangheluwe Peter2ORCID,Sepúlveda M. Rosario1ORCID

Affiliation:

1. Department of Cell Biology, Faculty of Sciences University of Granada Granada Spain

2. Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine KU Leuven Leuven Belgium

Abstract

AbstractMicroglia 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.

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3