The Pivotal Role of Intracellular Calcium in Oxaliplatin-Induced Inhibition of Neurite Outgrowth but Not Cell Death in Differentiated PC12 Cells

In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.

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Initiation and maintenance of NGF-stimulated neurite outgrowth requires activation of a phosphoinositide 3-kinase

Journal of Cell Science ◽

10.1242/jcs.109.2.289 ◽

1996 ◽

Vol 109 (2) ◽

pp. 289-300 ◽

Cited By ~ 3

Author(s):

T.R. Jackson ◽

I.J. Blader ◽

L.P. Hammonds-Odie ◽

C.R. Burga ◽

F. Cooke ◽

...

Keyword(s):

Neurite Outgrowth ◽

Pc12 Cells ◽

Specific Inhibitor ◽

Morphological Differentiation ◽

Sympathetic Neuron ◽

Neuronal Morphology ◽

Regulatory Subunit ◽

Membrane Reorganization ◽

Phosphoinositide 3 Kinase

Application of nerve growth factor (NGF) to PC12 cells stimulates a programme of physiological changes leading to the development of a sympathetic neuron like phenotype, one aspect of which is the development of a neuronal morphology characterised by the outgrowth of neuritic processes. We have investigated the role of phosphoinositide 3-kinase in NGF-stimulated morphological differentiation through two approaches: firstly, preincubation with wortmannin, a reputedly specific inhibitor of phosphoinositide kinases, completely inhibited initial morphological responses to NGF, the formation of actin filament rich microspikes and subsequent neurite outgrowth. This correlated with wortmannin inhibition of NGF-stimulated phosphatidylinositol(3,4,5)trisphosphate (PtdInsP3) and phosphatidylinositol(3,4)bisphosphate (PtdIns(3,4)P2) production and with inhibition of NGF-stimulated phosphoinositide 3-kinase activity in anti-phosphotyrosine immunoprecipitates. Secondly, the overexpression of a mutant p85 regulatory subunit of the phosphoinositide 3-kinase, which cannot interact with the catalytic p110 subunit, also substantially inhibited the initiation of NGF-stimulated neurite outgrowth. In addition, we found that wortmannin caused a rapid collapse of more mature neurites formed following several days exposure of PC12 cells to NGF. These results indicate that NGF-stimulated neurite outgrowth requires the activity of a tyrosine kinase regulated PI3-kinase and suggest that the primary product of this enzyme, PtdInsP3, is a necessary second messenger for the cytoskeletal and membrane reorganization events which occur during neuronal differentiation.

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Role of intracellular calcium concentration on tumor cell death from hyperthermia.

Oncology Reports ◽

10.3892/or.5.1.139 ◽

1998 ◽

Author(s):

Y Itagaki ◽

K Akagi ◽

M Uda ◽

Y Tanaka

Keyword(s):

Cell Death ◽

Tumor Cell ◽

Intracellular Calcium ◽

Calcium Concentration ◽

Intracellular Calcium Concentration ◽

Tumor Cell Death

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HCAR Is a Limitation Factor for Chlorophyll Cycle and Chlorophyll b Degradation in Chlorophyll-b-Overproducing Plants

Biomolecules ◽

10.3390/biom10121639 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1639

Author(s):

Xuan Zhao ◽

Ting Jia ◽

Xueyun Hu

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Metabolic Pathway ◽

Pivotal Role ◽

Limiting Factor ◽

Chlorophyll B ◽

Green Color ◽

Chl A ◽

Cycle Regulation

The chlorophyll (Chl) cycle is the metabolic pathway for Chl a and Chl b inter-conversion. In this pathway, Chl b is synthesized from Chl a by the catalyzing action of chlorophyllide a oxygenase (CAO). In contrast, Chl b is firstly reduced to produce 7-hydroxymethyl Chl (HMChl) a, which is catalyzed by two isozymes of Chl b reductase (CBR), non-yellow coloring 1 (NYC1) and NYC1-like (NOL). Subsequently, HMChl a is reduced to Chl a by HMChl a reductase (HCAR). CAO plays a pivotal role in Chl a/b ratio regulation and plants over-accumulate Chl b in CAO-overexpressing plants. NYC1 is more accumulated in Chl-b-overproducing plants, while HCAR is not changed. To investigate the role of HCAR in Chl cycle regulation, the Chl metabolites of Chl-b-overproducing plants were analyzed. The results showed that HMChl a accumulated in these plants, and it decreased and the Chl a/b ratio increased by overexpressing HCAR, implying HCAR is insufficient for Chl cycle in Chl-b-overproducing plants. Furthermore, during dark-induced senescence, the non-programmed cell death symptoms (leaves dehydrated with green color retained) of Chl-b-overproducing plants were obviously alleviated, and the content of HM pheophorbide (HMPheide) a and Pheide b were sharply decreased by overexpressing HCAR. These results imply that HCAR is also insufficient for Chl degradation in Chl-b-overproducing plants during senescence, thus causing the accumulation of Chl metabolites and non-programmed cell death of leaves. With these results taken together, we conclude that HCAR is not well regulated and it is a limiting factor for Chl cycle and Chl b degradation in Chl-b-overproducing plants.

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