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1.
Biol Reprod ; 106(3): 441-448, 2022 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-34791046

RESUMO

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.


Assuntos
Transporte Ativo do Núcleo Celular , Cálcio , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta , Fator de Transcrição RelA , Cálcio/metabolismo , Feminino , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/antagonistas & inibidores , Lipopolissacarídeos , Gravidez , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo
2.
Head Neck Pathol ; 18(1): 25, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526767

RESUMO

OBJECTIVE: To review tumors identified as "clear cell sarcoma" in order to determine similarities to the rare EWS fusion positive jaw and salivary gland tumors clear cell odontogenic carcinoma (CCOC) and clear cell carcinoma of the salivary gland (CCC). METHODS: PubMed was used to collect all reports of clear cell sarcoma (CCS). Search parameters were "clear cell sarcoma" and "CCS." References in the publications were screened and cross-referenced. Data extracted included demographic characteristics, presenting signs and symptoms, radiographic findings, histological and immunohistochemical features and known molecular/genetic aberrations. RESULTS: Clear cell sarcoma has several similarities to CCOC and CCC. All three tumor types have similar histologic appearances including the presence of clear cells, as well as similar genetic profiles in that all harbor an EWSR1-CREB family fusions. Additionally, these tumors appear in soft tissue as well as bone, and can have a prolonged clinical course. CCS can appear anywhere in the body, including the head and neck region. All three tumors appear to have a predilection to women, although CCS may have a slight younger age of onset as compared to CCOC and CCC (3rd vs 5th decade of life, respectively). CONCLUSION: Gaining a better understanding of the similarities and differences between these three tumors may lead to a better understanding of each one.


Assuntos
Carcinoma , Tumores Odontogênicos , Neoplasias das Glândulas Salivares , Sarcoma de Células Claras , Humanos , Feminino , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/metabolismo , Sarcoma de Células Claras/patologia , Proteína EWS de Ligação a RNA/genética , Tumores Odontogênicos/patologia , Neoplasias das Glândulas Salivares/genética , Proteínas de Fusão Oncogênica/genética
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