Abstract
Lymphocyte apoptosis is a hallmark of sepsis and contributes to disease mortality. In other acute injuries, such as myocardial and cerebral ischemia/reperfusion, apoptosis plays a significant role in disease-associated morbidity and mortality. We previously showed that constitutive activation of the potent antiapoptotic Akt/protein kinase B signaling pathway in lymphocytes both reduces sepsis-induced lymphocyte apoptosis and confers a significant survival advantage compared to wild-type littermates. Here, we demonstrate a therapeutic approach to acutely augment Akt activity in a wild-type animal. A cell-permeable peptide conjugated to the Akt-binding domain of the endogenous Akt coactivator, Tcl-1, prolongs Akt activity, activates extracellular regulated kinase (ERK) signaling and protects lymphocytes from numerous apoptotic stimuli both in vitro and in vivo. Molecular approaches to activate the antiapoptotic Akt and ERK signaling pathways may provide a novel tool to study these signaling pathways, as well as a new antiapoptotic strategy for the treatment of sepsis and other acute injuries.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 561-568 |
| Number of pages | 8 |
| Journal | FASEB Journal |
| Volume | 22 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2008 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Cell Biology
Cite this
Peptide-mediated activation of Akt and extracellular regulated kinase signaling prevents lymphocyte apoptosis. / McDunn, Jonathan E.; Muenzer, Jared T.; Rachdi, Latif; Chang, Katherine C.; Davis, Chris G.; Dunne, W. Michael; Piwnica-Worms, David; Bernal Mizrachi, Ernesto; Hotchkiss, Richard S.
In: FASEB Journal, Vol. 22, No. 2, 02.2008, p. 561-568.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Peptide-mediated activation of Akt and extracellular regulated kinase signaling prevents lymphocyte apoptosis
AU - McDunn, Jonathan E.
AU - Muenzer, Jared T.
AU - Rachdi, Latif
AU - Chang, Katherine C.
AU - Davis, Chris G.
AU - Dunne, W. Michael
AU - Piwnica-Worms, David
AU - Bernal Mizrachi, Ernesto
AU - Hotchkiss, Richard S.
PY - 2008/2
Y1 - 2008/2
N2 - Lymphocyte apoptosis is a hallmark of sepsis and contributes to disease mortality. In other acute injuries, such as myocardial and cerebral ischemia/reperfusion, apoptosis plays a significant role in disease-associated morbidity and mortality. We previously showed that constitutive activation of the potent antiapoptotic Akt/protein kinase B signaling pathway in lymphocytes both reduces sepsis-induced lymphocyte apoptosis and confers a significant survival advantage compared to wild-type littermates. Here, we demonstrate a therapeutic approach to acutely augment Akt activity in a wild-type animal. A cell-permeable peptide conjugated to the Akt-binding domain of the endogenous Akt coactivator, Tcl-1, prolongs Akt activity, activates extracellular regulated kinase (ERK) signaling and protects lymphocytes from numerous apoptotic stimuli both in vitro and in vivo. Molecular approaches to activate the antiapoptotic Akt and ERK signaling pathways may provide a novel tool to study these signaling pathways, as well as a new antiapoptotic strategy for the treatment of sepsis and other acute injuries.
AB - Lymphocyte apoptosis is a hallmark of sepsis and contributes to disease mortality. In other acute injuries, such as myocardial and cerebral ischemia/reperfusion, apoptosis plays a significant role in disease-associated morbidity and mortality. We previously showed that constitutive activation of the potent antiapoptotic Akt/protein kinase B signaling pathway in lymphocytes both reduces sepsis-induced lymphocyte apoptosis and confers a significant survival advantage compared to wild-type littermates. Here, we demonstrate a therapeutic approach to acutely augment Akt activity in a wild-type animal. A cell-permeable peptide conjugated to the Akt-binding domain of the endogenous Akt coactivator, Tcl-1, prolongs Akt activity, activates extracellular regulated kinase (ERK) signaling and protects lymphocytes from numerous apoptotic stimuli both in vitro and in vivo. Molecular approaches to activate the antiapoptotic Akt and ERK signaling pathways may provide a novel tool to study these signaling pathways, as well as a new antiapoptotic strategy for the treatment of sepsis and other acute injuries.
UR - http://www.scopus.com/inward/record.url?scp=38949168061&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38949168061&partnerID=8YFLogxK
U2 - 10.1096/fj.07-8283com
DO - 10.1096/fj.07-8283com
M3 - Article
C2 - 17855622
AN - SCOPUS:38949168061
VL - 22
SP - 561
EP - 568
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 2
ER -