Prevention of Programmed Cell Death of Sympathetic Neurons by the
            <i>bcl-2</i>
            Proto-Oncogene

García, Irene; Martinou, Isabelle; Tsujimoto, Yoshihide; Martinou, Jean‐Claude

doi:10.1126/science.1411528

Cited by 688 publications

(334 citation statements)

References 30 publications

(18 reference statements)

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“…We have shown previously that overexpression of bcl-2 in Grid2 Lc/ϩ olivary neurons will rescue most of the olivary neurons from target-related cell death (Zanjani et al, 1998b). This result is consistent with previous studies showing in vitro rescue of neurons from trophic factor withdrawal (Garcia et al, 1992;Allsopp et al, 1993;Batistatou et al, 1993) and in vivo rescue of neurons from axotomy or ischemia by bcl-2 overexpression Martinou et al, 1994;Farlie et al, 1995;Bonfanti et al, 1996;De Bilbao and Dubois-Dauphin, 1996) or deletion of Bax expression (Deckwerth et al, 1996;White et al, 1998).…”

Section: Granule Cell Survival and Olivary Neuron Deathsupporting

confidence: 82%

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

2000

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Lurcher is a gain-of-function mutation in the ␦2 glutamate receptor gene (Grid2) that turns the receptor into a leaky ion channel. The expression of the Lurcher gene in heterozygous (Grid2 Lc/ϩ ) mutants induces the death of almost all Purkinje cells starting from the second postnatal week. Ninety percent of the granule cells and 60-75% of the inferior olivary neurons die because of the loss of their target neurons, the Purkinje cells. The apoptotic nature of the neurodegeneration has been demonstrated previously by the presence of activated caspase-3 and DNA fragmentation. Bax, a pro-apoptotic gene of the Bcl-2 family, has been shown to be involved in developmental neuronal death. To study the role of Bax in Grid2 Lc/ϩ neurodegeneration, double mutants with Grid2 Lc/ϩ mice and Bax knock-out mice (BaxϪ/Ϫ) were generated. Bax deletion had no effect on the death of Purkinje cells and inferior olivary neurons, although a temporary rescue of some Purkinje cells could be detected in P15 Grid2 Lc/ϩ ;BaxϪ/Ϫ animals. From postnatal day 15 (P15) to P60, the number of granule cells in Grid2 Lc/ϩ ;BaxϪ/Ϫmice did not significantly change and was significantly increased compared with the number found in Grid2 Lc/ϩ ;Baxϩ/ϩ mice. Granule cell number in P60 Grid2 Lc/ϩ ;BaxϪ/Ϫ mice corresponded to 70% of the number found in wild-type mice. Our results show that Bax inactivation in Grid2 Lc/ϩ mice does not rescue intrinsic Purkinje cell death or the target-related cell death of olivary neurons, but Bax inactivation does inhibit persistently target-related cell death in cerebellar granule cells.

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Section: Granule Cell Survival and Olivary Neuron Deathsupporting

confidence: 82%

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

2000

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“…In vitro evidence that this gene could be involved in neuronal apoptosis comes from overexpression of this gene in neurons deprived of trophic factors (Garcia et al, 1992;Allsopp et al, 1993;Mah et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Apoptotic cell death induced by optic nerve lesion in the neonatal rat

et al. 1994

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Cell death can be ascribed to one of two distinct modes of degeneration: apoptosis (programmed or active cell death) or necrosis (passive degeneration). While apoptosis is generally assumed to occur in physiological conditions such as normal development or tissue turnover, necrotic cell degeneration is induced in pathological situations. Here we report that also in a pathological situation, such as after axotomy in the CNS, apoptotic type of cell death comes into play: following intracranial transection of the optic nerve in the neonatal rat in vivo, retinal ganglion cells undergo an active, apoptotic cell death. In fact, the administration of protein synthesis inhibitors (actinomycin D and cycloheximide) prevents the appearance of pyknotic nuclei as well as of fragmented DNA of ganglion cells at 24 hr postlesion. Correspondingly, the number of surviving cells after actinomycin D and cycloheximide treatment is comparable to normal, unlesioned retinas. In addition, cycloheximide decreases the number of pyknotic ganglion cells during spontaneous cell death.

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“…Recent studies of bcl-2 function in cultured postmitotic neurons have further established a role for this gene in the suppression of PCD, in complete absence of cell proliferation. Specifically, microinjection of bcl-2 expression plasmids into Nerve Growth Factor (NGF)-dependent sympathetic neurons and into NGF-dependent or brain-derived neurotrophic factor (BDNF)-dependent central nervous system (CNS)-derived sensory neurons has been shown to markedly delay the rate of cell death that occurs upon removal of the neurotrophic factors from cultures (Garcia et al, 1992;Allsopp et al, 1993). In contrast to the prolonged cell survival observed when elevations in the levels of Bcl-2 protein are achieved through gene transfer methods, antisense-mediated reductions in bcl-2 gene expression have been shown to accelerate the rate of cell death in the setting of growth factor withdrawal (Reed et al, 1990a,b), thus fulfilling another of Koch's postulates and confirming the importance of bcl-2 in the regulation of cell survival.…”

Section: Bcl-2 Blocks a Final Common Pathway:for Programmed Cell Deathmentioning

confidence: 99%

Bcl-2 and the regulation of programmed cell death

1994

The Journal of Cell Biology

2,168

1,250

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Prevention of Programmed Cell Death of Sympathetic Neurons by the bcl-2 Proto-Oncogene

Cited by 688 publications

References 30 publications

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

BaxInactivation in Lurcher Mutants Rescues Cerebellar Granule Cells But Not Purkinje Cells or Inferior Olivary Neurons

Apoptotic cell death induced by optic nerve lesion in the neonatal rat

Bcl-2 and the regulation of programmed cell death

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