Endothelin-3 induces hypertrophy of cardiomyocytes by the endogenous endothelin-1-mediated mechanism
| Autor: | Hiroshi Ito, Susumu Adachi, Hajime Akimoto, Mimi Tamamori, F Marumo, Michiaki Hiroe |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Endothelin Receptor Antagonists
medicine.medical_specialty Molecular Sequence Data Gene Expression Muscle Proteins Endogeny Biology Binding Competitive Peptides Cyclic Muscle hypertrophy Paracrine signalling Piperidines Internal medicine Gene expression medicine Animals RNA Messenger Northern blot Rats Wistar education Autocrine signalling Cells Cultured education.field_of_study Base Sequence Receptors Endothelin Endothelins Myocardium Hypertrophy General Medicine Oligonucleotides Antisense Endothelin 1 Actins Rats Endothelin 3 Endocrinology Animals Newborn Oligopeptides Research Article |
| Zdroj: | Journal of Clinical Investigation. 97:366-372 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci118424 |
| Popis: | We have recently reported that endothelin-1 (ET-1) mediates angiotensin II-induced hypertrophy of cardiomyocytes as an autocrine/paracrine factor. In the present study, we examined whether endothelin-3 (ET-3) induces hypertrophy of cultured neonatal rat cardiomyocytes and whether endogenous ET-1 mediates this effect. ET-3 (10(-7) M) increased the cell surface area of cardiomyocytes after 48 h. ET-3 dose dependently (10(-9)-10(-7) M) stimulated protein synthesis as evaluated by [3H]leucine incorporation; the maximum response was 1.4-fold increase over the control at 10(-7) M. Since the response of cardiac hypertrophy is characterized by enhanced expression of fetal isoforms of muscle specific genes, the effect of ET-3 on steady state levels of mRNA for skeletal alpha-actin was evaluated by Northern blot analysis. ET-3 (10(-9)-10(-7) M) increased mRNA level for skeletal alpha-actin with a maximum response after 6 h. ET-3-induced [3H]leucine incorporation, skeletal alpha-actin mRNA and cell surface area were inhibited by a synthetic ETB receptor antagonist (BQ788). Interestingly, ET-3-induced skeletal alpha-actin gene expression and [3H]leucine incorporation were inhibited by a synthetic ETA receptor antagonist (BQ123) as well as by antisense oligonucleotides against peproET-1 mRNA. ET-3 (10(-7) M) transiently increased mRNA levels for ET-1 peaking at 30 min and stimulated the release of immunoreactive ET-1 from cardiomyocytes. These results suggest that endogenous ET-1 locally generated and secreted by cardiomyocytes may contribute to ET-3-induced cardiac hypertrophy as an autocrine/paracrine factor. |
| Databáze: | OpenAIRE |
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