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Distinct protein kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes.
Kebbe, Mariana; Naud, Patrice; Assous, Ines; Gagnon, Emmanuelle; McCall, Anthony; Villeneuve, Louis; Leblanc, Charles Alexandre; Nguyen, Quang Trinh; Calderone, Angelino.
Afiliación
  • Kebbe M; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • Naud P; Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, Quebec, Canada.
  • Assous I; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • Gagnon E; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • McCall A; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • Villeneuve L; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • Leblanc CA; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • Nguyen QT; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
  • Calderone A; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
Am J Physiol Cell Physiol ; 325(2): C406-C419, 2023 08 01.
Article en En | MEDLINE | ID: mdl-36745530
The present study tested the hypothesis that protein kinase C-α (PKC-α) recruitment in the presence of the p38α/ß MAPK inhibitor SB203580 facilitated the appearance and cell cycle re-entry of nestin(+)-neonatal rat ventricular cardiomyocytes (NNVMs) and induced a transcript profile delineating a proliferative phenotype. Phorbol 12,13-dibutyrate (PDBu) treatment did not induce de novo nestin expression or increase the cell cycle re-entry of 1-day-old NNVMs but significantly increased runt-related transcription factor 1 (Runx1) and p16 cell cycle inhibitor (CDKN2a) mRNA levels and downregulated epithelial cell transforming 2 (ECT2) mRNA expression. SB203580 administration to PDBu-treated NNVMs induced de novo nestin expression, preferentially increased the density (normalized to 500 NNVMs) of nestin(+)-NNVMs that incorporated 5-bromo-2'-deoxyuridine (PDBu, 1.4 ± 3 vs. PDBu/SB203580, 128 ± 34; n = 5 independent litters), significantly inhibited CDKN2a and Runx1 mRNA upregulation and reversed ECT2 mRNA downregulation. PDBu treatment of NNVMs reduced PKC-α, protein kinase-δ (PKC-δ) and protein kinase-ε (PKC-ε) protein levels and GF109203X (conventional PKC isoform inhibitor) selectively attenuated PKC-α protein downregulation. GF109203X administration to PDBu/SB203580-treated NNVMs significantly reduced the density of nestin(+)-NNVMs that incorporated 5-bromo-2'-deoxyuridine (PDBu/SB203580/GF109203X, 40 ± 46; n = 5). Moreover, GF109203X/PDBu/SB203580 treatment unmasked the predominant appearance of a separate NNVM population that incorporated 5-bromo-2'-deoxyuridine (PDBu/SB203580/GF109203X, 192 ± 42; n = 5) delineated by the absence of de novo nestin expression. Sotrastaurin (conventional/novel PKC isoform inhibitor) administration to PDBu/SB203580-treated NNVMs significantly attenuated the density of nestin(+)-NNVMs (PDBu/SB203580/sotrastaurin, 8 ± 10; n = 4) and nestin(-)-NNVMs (PDBu/SB203580/sotrastaurin, 64 ± 30; n = 4) that incorporated 5-bromo-2'-deoxyuridine. These data reveal that the neonatal rat heart contains at least two separate populations of NNVMs that re-enter the cell cycle and the preferential appearance of nestin(+)- or nestin(-)-NNVMs is driven by distinct PKC isoforms in the presence of SB203580.NEW & NOTEWORTHY The appearance of nestin(+)-neonatal rat ventricular cardiomyocytes that re-entered the cell cycle following phorbol ester stimulation in the presence of p38α/ß MAPK inhibitor SB203580 was associated with the inhibition of Runx1 and CDKN2a mRNA upregulation. PKC-α selectively induced the cell cycle re-entry of nestin(+)-neonatal rat ventricular cardiomyocytes. Pharmacological inhibition of PKC-α with concomitant p38α/ß MAPK suppression unmasked the cell cycle re-entry of a second population of neonatal rat ventricular cardiomyocytes in the absence of nestin expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Quinasa C / Miocitos Cardíacos Límite: Animals Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Quinasa C / Miocitos Cardíacos Límite: Animals Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Canadá
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