Thyroid Hormone Upregulates Cav1.2 Channels in Cardiac Cells via the Downregulation of the Channels' ß4 Subunit.

Carrillo, Elba D; Alvarado, Juan A; Hernández, Ascención; Lezama, Ivonne; García, María C; Sánchez, Jorge A

Carrillo, Elba D; Alvarado, Juan A; Hernández, Ascención; Lezama, Ivonne; García, María C; Sánchez, Jorge A.

Afiliação

Carrillo ED; Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico.
Alvarado JA; Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico.
Hernández A; Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico.
Lezama I; Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico.
García MC; Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico.
Sánchez JA; Department of Pharmacology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico.

Int J Mol Sci ; 25(19)2024 Oct 08.

Article em En | MEDLINE | ID: mdl-39409130

ABSTRACT

ABSTRACT

Thyroid hormone binds to specific nuclear receptors, regulating the expression of target genes, with major effects on cardiac function. Triiodothyronine (T3) increases the expression of key proteins related to calcium homeostasis, such as the sarcoplasmic reticulum calcium ATPase pump, but the detailed mechanism of gene regulation by T3 in cardiac voltage-gated calcium (Cav1.2) channels remains incompletely explored. Furthermore, the effects of T3 on Cav1.2 auxiliary subunits have not been investigated. We conducted quantitative reverse transcriptase polymerase chain reaction, Western blot, and immunofluorescence experiments in H9c2 cells derived from rat ventricular tissue, examining the effects of T3 on the expression of α1c, the principal subunit of Cav1.2 channels, and Cavß4, an auxiliary Cav1.2 subunit that regulates gene expression. The translocation of phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB) by T3 was also examined. We found that T3 has opposite effects on these channel proteins, upregulating α1c and downregulating Cavß4, and that it increases the nuclear translocation of pCREB while decreasing the translocation of Cavß4. Finally, we found that overexpression of Cavß4 represses the mRNA expression of α1c, suggesting that T3 upregulates the expression of the α1c subunit in response to a decrease in Cavß4 subunit expression.

Assuntos

Canais de Cálcio Tipo L; Miócitos Cardíacos; Animais; Canais de Cálcio Tipo L/metabolismo; Canais de Cálcio Tipo L/genética; Ratos; Miócitos Cardíacos/metabolismo; Miócitos Cardíacos/efeitos dos fármacos; Tri-Iodotironina/farmacologia; Tri-Iodotironina/metabolismo; Regulação para Baixo/efeitos dos fármacos; Hormônios Tireóideos/metabolismo; Linhagem Celular; Regulação para Cima/efeitos dos fármacos; Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo; Regulação da Expressão Gênica/efeitos dos fármacos; Subunidades Proteicas/metabolismo; Subunidades Proteicas/genética

Palavras-chave

Cav1.2 channels; H9c2 cell line; pCREB; thyroid hormone; ß4 subunit

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canais de Cálcio Tipo L / Miócitos Cardíacos Limite: Animals Idioma: En Revista: Int J Mol Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Suíça

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