{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kent LN"],"funding":["NICHD NIH HHS","National Institutes of Health","NIH HHS","Washington University Department of Obstetrics and Gynecology"],"pagination":["441-448"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8934693"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["106(3)"],"pubmed_abstract":["Nuclear factor kappa B (NF-κB) transcriptionally regulates several genes involved in initiating uterine contractions. A key factor controlling NF-κB activity is its translocation to the nucleus. In myometrial smooth muscle cells (MSMCs), this translocation can be stimulated by the inflammatory molecule lipopolysaccharide (LPS) or by blocking the potassium calcium-activated channel subfamily M alpha 1 (KCNMA1 or BKCa) with paxilline (PAX). Here, we sought to determine the mechanism by which blocking BKCa causes NF-κB-p65 translocation to the nucleus in MSMCs. We show that LPS- and PAX-induced NF-κB-p65 translocation are similar in that neither depends on several mitogen-activated protein kinase pathways, but both require increased intracellular calcium (Ca2+). However, the nuclear transport inhibitor wheat germ agglutinin prevented NF-κB-p65 nuclear translocation in response to LPS but not in response to PAX. Blocking BKCa located on the plasma membrane resulted in a transient NF-κB-p65 nuclear translocation that was not sufficient to induce expression of its transcriptional target, suggesting a role for intracellular BKCa. We report that BKCa also localizes to the nucleus and that blocking nuclear BKCa results in an increase in nuclear Ca2+ in MSMCs. Together, these data suggest that BKCa localized on the nuclear membrane plays a key role in regulating nuclear Ca2+ and NF-κB-p65 nuclear translocation in MSMCs."],"journal":["Biology of reproduction"],"pubmed_title":["Blocking the BKCa channel induces NF-κB nuclear translocation by increasing nuclear calcium concentration†."],"pmcid":["PMC8934693"],"funding_grant_id":["R01 HD037831"],"pubmed_authors":["England SK","Kent LN","Li Y","Weil SG","Wakle-Prabagaran M","Naqvi MZ"],"additional_accession":[]},"is_claimable":false,"name":"Blocking the BKCa channel induces NF-κB nuclear translocation by increasing nuclear calcium concentration†.","description":"Nuclear factor kappa B (NF-κB) transcriptionally regulates several genes involved in initiating uterine contractions. A key factor controlling NF-κB activity is its translocation to the nucleus. In myometrial smooth muscle cells (MSMCs), this translocation can be stimulated by the inflammatory molecule lipopolysaccharide (LPS) or by blocking the potassium calcium-activated channel subfamily M alpha 1 (KCNMA1 or BKCa) with paxilline (PAX). Here, we sought to determine the mechanism by which blocking BKCa causes NF-κB-p65 translocation to the nucleus in MSMCs. We show that LPS- and PAX-induced NF-κB-p65 translocation are similar in that neither depends on several mitogen-activated protein kinase pathways, but both require increased intracellular calcium (Ca2+). However, the nuclear transport inhibitor wheat germ agglutinin prevented NF-κB-p65 nuclear translocation in response to LPS but not in response to PAX. Blocking BKCa located on the plasma membrane resulted in a transient NF-κB-p65 nuclear translocation that was not sufficient to induce expression of its transcriptional target, suggesting a role for intracellular BKCa. We report that BKCa also localizes to the nucleus and that blocking nuclear BKCa results in an increase in nuclear Ca2+ in MSMCs. Together, these data suggest that BKCa localized on the nuclear membrane plays a key role in regulating nuclear Ca2+ and NF-κB-p65 nuclear translocation in MSMCs.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2025-04-04T09:02:33.311Z","creation":"2025-04-04T09:02:33.311Z"},"accession":"S-EPMC8934693","cross_references":{"pubmed":["34791046"],"doi":["10.1093/biolre/ioab211"]}}