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Titolo:
EXPRESSION OF THE CYCLIC-AMP-DEPENDENT PROTEIN-KINASE (PKA) CATALYTICSUBUNIT FROM A HERPES-SIMPLEX VIRUS VECTOR EXTENDS THE SURVIVAL OF RAT SYMPATHETIC NEURONS IN THE ABSENCE OF NGF
Autore:
BUCKMASTER EA; TOLKOVSKY AM;
Indirizzi:
UNIV OXFORD,DEPT PHYSIOL,PARKS RD OXFORD OX1 3PT ENGLAND UNIV OXFORD,DEPT HUMAN ANAT OXFORD OX1 3QX ENGLAND
Titolo Testata:
European journal of neuroscience
fascicolo: 8, volume: 6, anno: 1994,
pagine: 1316 - 1327
SICI:
0953-816X(1994)6:8<1316:EOTCP(>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; BETA-GALACTOSIDASE; THYMIDINE KINASE; GENE-TRANSFER; RNA-SYNTHESIS; TYPE-1; CELLS; GLUCOCORTICOIDS; REPLICATION; RECEPTOR;
Keywords:
C-FOS; HSV-1; NERVE GROWTH FACTOR; RAT SUPERIOR CERVICAL GANGLION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
E.A. Buckmaster e A.M. Tolkovsky, "EXPRESSION OF THE CYCLIC-AMP-DEPENDENT PROTEIN-KINASE (PKA) CATALYTICSUBUNIT FROM A HERPES-SIMPLEX VIRUS VECTOR EXTENDS THE SURVIVAL OF RAT SYMPATHETIC NEURONS IN THE ABSENCE OF NGF", European journal of neuroscience, 6(8), 1994, pp. 1316-1327

Abstract

Superior cervical ganglion neurons from neonatal rats are dependent on nerve growth factor for their survival both in vivo and in vitro. Inculture this requirement can be largely replaced by cAMP or its analogues. Since activation of protein kinase A by cAMP is likely to be thepathway by which it exerts its survival-promoting effect, we have tested the feasibility of using herpes simplex virus (HSV) as a vector for expressing survival-promoting genes in neurons by cloning the catalytic subunit of the cAMP-dependent protein kinase (PKAcat) with a metallothionein gene promoter into the HSV thymidine kinase gene by homologous recombination. About 95% of the neurons became infected using 2.5 p.f.u. per cell. When this construct was used to express PKAcat in superior cervical ganglion neurons, in the presence of nerve growth factor (NGF) increases of 1.9- to 2.4-fold in PKA activity were found 8-10 h after infection; levels remained elevated (1.4- to 2.1-fold) up to 18 h, returning to basal by 24 h. After infection in the absence of NGF, cumulative activity over 24 h was similar to 3.5-fold lower in the first 24 h. Although the level of the inhibitory regulatory subunit type I was raised by 18 h, this is unlikely to completely explain the transient activity of PKAcat. When neurons were induced to express maximum PKAcat levels in the presence of NGF and then deprived of NGF, survival was extended by up to 2 days, demonstrating a direct role for PKA in promoting survival. By this time, some neurite degeneration was beginning which appeared to be partly due to toxic effects of the virus. However, replenishment with NGF supported further survival, showing that at this time the neurons were still viable. Similar rates of survival were obtained using a tsK-based PKAcat vector, but no significant survival was obtained with parental HSV or tsK virus strains. These data demonstrate the feasibility, and highlight some of the problems, of using HSV-based vectors as tools for expressing functional survival proteins in sympathetic neurons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/08/20 alle ore 23:03:32