Physiological stress and nerve growth factor treatment regulate stress-activated protein kinase activity in PC12 cells

Goodman, M. Nadine; Reigh, Clint; Landreth, Gary E.

doi:10.1002/(sici)1097-4695(19980915)36:4<537::aid-neu7>3.0.co;2-x

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…3A, B, and D). As has been described elsewhere (Goodman et al, 1998), the basal level of JNK activity is lower in naive compared with differentiated PC12 cells. CEP-1347 substantially suppresses JNK1 activation at concentrations of 300 -1,000 nM (Fig.…”

Section: Cep-1347 Blocks Jnk Activation In Pc12 Cells Deprived Of Trosupporting

confidence: 61%

“…5). It has been reported that stimulation of process outgrowth in PC12 cultures by staurosporine or NGF is associated with an increase in JNK activity, and, on this basis, it has been suggested that JNKs may play a role in formation and growth of neurites (Heasley et al, 1996;Yao et al, 1997;Eilers et al, 1998;Goodman et al, 1998). Taken together, these observations raise the possibility that CEP-1347 may delay neurite initiation and regeneration by lowering the prolonged NGF-induced JNK activation.…”

Section: Discussionmentioning

confidence: 88%

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CEP‐1347 (KT7515), an Inhibitor of JNK Activation, Rescues Sympathetic Neurons and Neuronally Differentiated PC12 Cells from Death Evoked by three Distinct Insults

1999

Journal of Neurochemistry

176

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Section: Cep-1347 Blocks Jnk Activation In Pc12 Cells Deprived Of Trosupporting

confidence: 61%

Section: Discussionmentioning

confidence: 88%

CEP‐1347 (KT7515), an Inhibitor of JNK Activation, Rescues Sympathetic Neurons and Neuronally Differentiated PC12 Cells from Death Evoked by three Distinct Insults

1999

Journal of Neurochemistry

176

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“…The activation of JNKs after NGF treatment in PC12 cells has already been described (23,25,56), but so far, its meaning is completely unknown. Our finding of the differentiation-triggering role of the JNK3 isoform, however, strikingly counteracts the widely accepted role of JNK3 as a pro-degenerative effector molecule (10,18).…”

Section: Jnk3 Promotes Neuronal Differentiationmentioning

confidence: 98%

A Single c-Jun N-terminal Kinase Isoform (JNK3-p54) Is an Effector in Both Neuronal Differentiation and Cell Death

Waetzig

Herdegen

2003

Journal of Biological Chemistry

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The c-Jun N-terminal kinases (JNKs) mediate degeneration and apoptosis in the brain. Particularly, JNK3 is considered to be a degenerative enzyme with c-Jun as a relevant substrate. The contribution of individual JNK isoforms, however, to pathological as well as to physiological processes remains to be defined. To analyze the effects of a single JNK isoform on neuronal cell death and differentiation, we transfected PC12 cells, which normally express only JNK1 and JNK2, with JNK3-p54. Transfected JNK3 significantly enhanced cell death after UV irradiation (0.5-6 J/cm(2)) and paclitaxel/taxol treatment (1-10 microm). In contrast, in the context of nerve growth factor-induced (10 or 50 ng/ml) differentiation of PC12 cells, JNK3 expression significantly increased the number and length of neurites. This functional dichotomy of JNK3 was mirrored by differential activation and induction of nuclear JNK substrates; although activating transcription factor-2 phosphorylation was enhanced by death signaling in response to UV and taxol, c-Jun protein expression and N-terminal phosphorylation were increased during nerve growth factor-induced differentiation. The absence of significant JNK activation or target phosphorylation in response to H(2)O(2) (60 microm) further supports the hypothesis that JNK isoforms are not merely injury- or stress-specific kinases but also have context-specific physiological functions.

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“…36 JNK/SAPKs are also strongly activated during stressful conditions such as serum withdrawal. 37,38 In order to test if the ceramide-JNK/SAPKs pathway was involved in our system, E6-1 S and E6-1 R2 clones c8, c12 and c45 were incubated for 10 h with 30 mM of C 2 -ceramide or under serum free conditions for 48 h. After treatment, cells were harvested, washed, lysed and JNK/SAPKs activation was tested by Western blot with antibodies directed against active JNK. Both C 2 -ceramide treatment and serum free conditions induced increased JNK/SAPKs activity in E6-1 S cells, as shown in Figure 5.…”

Section: Activation Of Jnk/sapks After Ceramide Treatment Serum Starmentioning

confidence: 99%

Fas, ceramide and serum withdrawal induce apoptosis via a common pathway in a type II Jurkat cell line

2002

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Ceramide is a key mediator of apoptosis, yet its role in Fasmediated apoptosis is controversial. Some reports have indicated that ceramide is either a primary signaling molecule in Fas-induced cell death, or that it functions upstream of Fas by increasing FasL expression. Other studies have suggested that ceramide is not relevant to Fas-induced cell death. We have approached this problem by studying ceramide-induced apoptosis in unique Jurkat cell clones selected for resistance to membrane-bound FasL-induced death. Resistance of the mutant Jurkat cells was specific for FasL killing, since the mutant clones were sensitive to other apoptotic stimuli such as cycloheximide and staurosporine. We tested the effects of serum withdrawal, one of the strongest inducers of ceramide, and of exogenous ceramide on apoptosis of both wild-type and FasL-resistant clones. Wild-type Jurkat cells were remarkably sensitive to serum withdrawal and to exogenous ceramide. In contrast all FasL-resistant mutant clones were resistant to these apoptosis-inducing conditions. In contrast to previous work, we did not detect an increase in FasL in either wild-type or mutant clones. Moreover activation of stressactivated protein kinases (JNK/SAPKs) after serum withdrawal and exogenous ceramide treatment was detected only in the wild-type and not in the resistant clones. Because of the parallel resistance of the mutant clones to Fas and to ceramide-induced apoptosis, our data support the notion that ceramide is a second messenger for the Fas/FasL pathway and that serum withdrawal, through production of ceramide, shares a common step with the Fas-mediated apoptotic pathway. Finally, our data suggest that activation of JNK/ SAPKs is a common mediator of the three pathways tested.

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Physiological stress and nerve growth factor treatment regulate stress-activated protein kinase activity in PC12 cells

Cited by 8 publications

References 13 publications

CEP‐1347 (KT7515), an Inhibitor of JNK Activation, Rescues Sympathetic Neurons and Neuronally Differentiated PC12 Cells from Death Evoked by three Distinct Insults

CEP‐1347 (KT7515), an Inhibitor of JNK Activation, Rescues Sympathetic Neurons and Neuronally Differentiated PC12 Cells from Death Evoked by three Distinct Insults

A Single c-Jun N-terminal Kinase Isoform (JNK3-p54) Is an Effector in Both Neuronal Differentiation and Cell Death

Fas, ceramide and serum withdrawal induce apoptosis via a common pathway in a type II Jurkat cell line

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