Effects of Docosahexaenoic and Arachidonic Acids on the Synthesis and Distribution of Aminophospholipids during Neuronal Differentiation of PC12 Cells

Ikemoto, Atsushi; Kobayashi, Tetsuyuki; Emoto, Kazuo; Umeda, Masato; Watanabe, Shiro; Okuyama, Harumi

doi:10.1006/abbi.1999.1110

Cited by 43 publications

(25 citation statements)

References 35 publications

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“…The first one proposes that the increased levels of PtdCho attained by the engineered cell lines could have a structural function, providing a platform for cytoskeletal or signaling proteins to promote differentiation. Favoring this mechanism, and considering that polyunsaturated fatty acids represent 50% of the fatty acids in the plasma membrane phospholipids of neurons, previous work has demonstrated a significant increase in neurite length when neuronal cells are differentiated in media supplemented with the polyunsaturated fatty acids, arachidonic acid, or docosahexaenoic acid (52)(53)(54)(55). Similarly, overexpression of acyl-CoA synthetase 2, which ligates free fatty acids to a coenzyme A carrier, stimulates fatty acid uptake, enhances lipid synthesis, and promotes neurite lengthening (56).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylcholine Biosynthesis during Neuronal Differentiation and Its Role in Cell Fate Determination

Marcucci

Paoletti

Jackowski

et al. 2010

Journal of Biological Chemistry

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Neuronal differentiation is characterized by neuritogenesis and neurite outgrowth, processes that are dependent on membrane biosynthesis. Thus, the production of phosphatidylcholine (PtdCho), the major membrane phospholipid, should be stimulated during neuronal differentiation. We demonstrate that during retinoic acid (RA)-induced differentiation of Neuro-2a cells, PtdCho synthesis was promoted by an ordered and sequential activation of choline kinase ␣ (CK␣) and choline cytidylyltransferase ␣ (CCT␣). Early after RA stimulation, the increase in PtdCho synthesis is mainly governed by the biochemical activation of CCT␣. Later, the transcription of CK␣-and CCT␣-encoding genes was induced. Both PtdCho biosynthesis and neuronal differentiation are dependent on ERK activation. A novel mechanism is proposed by which PtdCho biosynthesis is coordinated during neuronal differentiation. Enforced expression of either CK␣ or CCT␣ increased the rate of synthesis and the amount of PtdCho, and these cells initiated differentiation without RA stimulation, as evidenced by cell morphology and the expression of genes associated with neuritogenesis. The differentiation resulting from enforced expression of CCT␣ or CK␣ was dependent on persistent ERK activation. These results indicate that elevated PtdCho synthesis could mimic the RA signals and thus determine neuronal cell fate. Moreover, they could explain the key role that PtdCho plays during neuronal regeneration.

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Section: Discussionmentioning

confidence: 99%

Phosphatidylcholine Biosynthesis during Neuronal Differentiation and Its Role in Cell Fate Determination

Marcucci

Paoletti

Jackowski

et al. 2010

Journal of Biological Chemistry

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“…These ®ndings in part suggest a necessity for DHA, and hence sucient dietary consumption by the mother, that can be utilized by the developing fetus. Furthermore, reports have shown the importance of DHA during gliogenesis [55,56]. Ikemoto et al [55,56], found using PC12 cells that DHA promotes neurite outgrowth, in contrast to AA which suppresses this process.…”

Section: Membrane Structure and Function: Relation To Fatty Acid Pro®lementioning

confidence: 99%

“…Furthermore, reports have shown the importance of DHA during gliogenesis [55,56]. Ikemoto et al [55,56], found using PC12 cells that DHA promotes neurite outgrowth, in contrast to AA which suppresses this process. They hypothesised that decreased phospholipid synthesis, in particular PE by arachidonic acid may lead to the suppression of neurite growth.…”

Section: Membrane Structure and Function: Relation To Fatty Acid Pro®lementioning

confidence: 99%

Essential fatty acids and the brain: possible health implications

Youdim

Martín

Joseph

2000

Intl J of Devlp Neuroscience

430

273

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Linoleic and a-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions aecting membrane¯uidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs re¯ect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit. Published by Elsevier Science Ltd.

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“…Because cerebral cortex plays the crucial role in the memory function and the cerebral neurite elongation involves an expansion of the cell surface membrane, and newly synthesized membrane materials such as PLs and proteins must be supplied to the growing neurite [16], in the present study, therefore, the cerebral cortical cells from embryonic day 18 (E-18) rat embryos were selected to examine the neuronal cell viability, the neurite outgrowth and the changes in the growth-associated protein-43 (GAP-43) immunoactivity, the discrete PL contents and the fatty acid composition of the PL species after different periods of DHA exposure in vitro, which makes us to investigate the effects of DHA on the cortical neuron development and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures

Cao

Xue

et al. 2005

The Journal of Nutritional Biochemistry

102

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Effects of Docosahexaenoic and Arachidonic Acids on the Synthesis and Distribution of Aminophospholipids during Neuronal Differentiation of PC12 Cells

Cited by 43 publications

References 35 publications

Phosphatidylcholine Biosynthesis during Neuronal Differentiation and Its Role in Cell Fate Determination

Phosphatidylcholine Biosynthesis during Neuronal Differentiation and Its Role in Cell Fate Determination

Essential fatty acids and the brain: possible health implications

Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures

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