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Identification des voies de MAPK activées par la surexpression du récepteur [alpha]₁-adrénergique dans le coeur de souris
| Content Provider | Semantic Scholar |
|---|---|
| Author | Benoît, Marie-Josée |
| Copyright Year | 2005 |
| Abstract | Cardiomyocyte-specific overexpression of the wild-type a IB-adrenergic receptor (ai B AR) produces a slowly progressing cardiomyopathy associated with clinical signs of heart failure and premature death around middle age (Lemire et al., 2001, Cardiac directed overexpression of wild-type a 1B-adrenergic receptor induces dilated cardiomyopathy, Am. J. Physiol. 281: H931—H938). In the heart, aj-AR activate the ERK MAPK cascade. The aim of this project was to determine if cardiac-specific overexpression of the wild-type UIB-AR resuits in sustained activation of the ERK pathway. At 3 and 9 mo ERK activity was increased in alB-AR overexpressing hearts relative to non-transgenic animais. Similarly, phosphorylation of MEK and 90rsk were also elevated. MAP kinase phosphatases (MKPs), which inactivate MAP kinases, are transcriptionally regulated. MKP2 mRNA levels were reduced at 3 mo in alB-AR overexpressing hearts. Interestingly, there was a general trend for reduced expression of MKP-1, -2, and -3 with increased age. In addition, expression of the modulatory calcineurin-interacting protein (MCIP) 1, an indicator of calcineurin activity, was elevated 3-fold in ŒIB-AR overexpressing hearts at both 3 and 9 mos. These resuits indicate that the overexpression of the wild-type alB-AR leads to chronic changes in the activation of signalling pathways previously shown to be associated with the hypertrophic response. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/15188/Benoit_Marie-Josee_2004_memoire.pdf?isAllowed=y&sequence=1 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
