Premium
Altered MAP kinases and Akt activation during compensated eccentric cardiac hypretrophy
Author(s) -
Haddad Georges E.,
Alvin Zikiar,
Laurence Graham G.,
Teos Leyla Y
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.49
Subject(s) - protein kinase b , p38 mitogen activated protein kinases , endocrinology , medicine , ly294002 , kinase , mapk/erk pathway , phosphorylation , muscle hypertrophy , chemistry , biochemistry
The role of MAPK and PI 3K in the transduction of ANG II signaling during the development of cardiac hypertrophy was investigated. Eccentric cardiac hypertrophy was induced in adult rats by 3 weeks A‐V shunt. Hearts were retrogradely perfused for 20 min with either Tyrode alone (control), with ANG II (10 −7 M), or with respective kinase inhibitor (10 −6 M) in the presence or absence of ANG II (10 −7 M). Shunted hearts had a 33% increase in relative heart weight. Western blot analysis showed that shunted hearts had higher activation levels for ERK1 (56%), ERK2 (227%), p38 (75%) and Akt (67%). In normal hearts, ANG II increased ERK1, ERK2 and p38 MAPK phosphorylation by 57%, 196%, 94%, respectively. However in the hypertrophied hearts, ANG II did not. Treatment with either inhibitor for ERK1/2 (PD98059), p38 (SB203580) or Akt (LY294002) did not affect the activation level of the respective kinase in the normal hearts, but reduced it to sham ones in the hypertrophied hearts. In both groups, p38 MAPK inhibition induced a cross‐activation of ERK1/2, but reduced Akt activation in the shunt. However, Akt inhibition reduced ERK1/2 activation levels in the shunted hearts. Thus eccentric hypertrophy exhibits: (1) elevated MAPKs and Akt activity; (2) blunted activation of MAPKs to ANG II; and (3) altered cross‐activation between MAPK and Akt. This work was supported in part by grants GM08016‐36 from NIGMS/NIH and 2G12 RR003048 RCMI, NCRR/NIH .