Microtubular stability affects cardiomyocyte glycolysis by HIF-1alpha expression and endonuclear aggregation during early stages of hypoxia.
Am J Physiol Heart Circ Physiol
; 298(6): H1919-31, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20228255
ABSTRACT
Hypoxia-inducible factor (HIF)-1alpha is a key regulator of anaerobic energy metabolism. We asked the following question Does the breakdown of microtubular structures influence glycolysis in hypoxic cardiomyocytes by regulating HIF-1alpha? Neonatal rat cardiomyocytes were cultured under hypoxic conditions, while microtubule-stabilizing (paclitaxel) and -depolymerizing (colchicine) agents were used to change microtubular structure. Models of high microtubule-associated protein 4 (MAP4) expression and RNA interference of microtubulin expression were established. Microtubular structural changes and intracellular HIF-1alpha protein distribution were observed with laser confocal scanning microscopy. Content of key glycolytic enzymes, viability, and energy content of cardiomyocytes were determined by colorimetry and high-performance liquid chromatography. HIF-1alpha protein content and mRNA expression were determined by Western blotting and real-time PCR, respectively. Low doses of microtubule-stabilizing agent (10 mumol/l paclitaxel) and enhanced expression of MAP4 stabilized the reticular microtubular structures in hypoxic cardiomyocytes, increased the content of key glycolytic enzymes, ameliorated energy supply and enhanced cell viability, and upregulated HIF-1alpha protein expression and endonuclear aggregation. In contrast, the microtubule-depolymerizing agent (10 mumol/l colchicine) or reduced microtubulin expression had adverse affects on the same parameters, in particular, HIF-1alpha protein content and endonuclear aggregation. We conclude that microtubular structural changes influence glycolysis in the early stages of hypoxia in cardiomyocytes by regulating HIF-1alpha content. Stabilizing microtubular structures increases endonuclear and total HIF-1alpha expression, content of key glycolytic enzymes, and energy supply. These findings provide potential therapeutic targets for ameliorating cell energy metabolism during early myocardial hypoxia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Núcleo Celular
/
Miócitos Cardíacos
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Glicólise
/
Hipóxia
/
Microtúbulos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Heart Circ Physiol
Assunto da revista:
CARDIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
China