Raf-1 Kinase Inhibitory Protein (RKIP) Promotes Retinal Ganglion Cell Survival and Axonal Regeneration Following Optic Nerve Crush

Wei, Jie; Jiang, Hua; Gao, Hongrui; Wang, Guangjie

doi:10.1007/s12031-015-0612-8

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…6 ). A possible explanation is based on the role of RKIP, a member of the PEBP (PtdEtn binding protein), as a negative regulator of Raf-1 and MEK 42 – 44 . Perhaps the binding of PtdEtn to RKIP might induce conformational changes that disrupt its interaction with Raf and MEK, leading to ERK activation and thus, astroglial differentiation 42 , 23 , 45 .…”

Section: Discussionmentioning

confidence: 99%

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Montaner

Santana

Schroeder

et al. 2018

Sci Rep

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Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.

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Section: Discussionmentioning

confidence: 99%

Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

Montaner

Santana

Schroeder

et al. 2018

Sci Rep

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“…PE (42:8), was also included in group C in this study. It is associated with Raf-1 kinase inhibitory protein (RKIP), which functions to promote RGC survival and axonal regeneration after NC in mice 57 . It is possible that elevated PE (42:8) is also part of a protective response in injured RGCs after NC.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic changes in the mouse retina after optic nerve injury

Sato

Saigusa

Saito

et al. 2018

Sci Rep

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In glaucoma, although axonal injury drives retinal ganglion cell (RGC) death, little is known about the underlying pathomechanisms. To provide new mechanistic insights and identify new biomarkers, we combined latest non-targeting metabolomics analyses to profile altered metabolites in the mouse whole retina 2, 4, and 7 days after optic nerve crush (NC). Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography Fourier transform mass spectrometry covering wide spectrum of metabolites in combination highlighted 30 metabolites that changed its concentration after NC. The analysis displayed similar changes for purine nucleotide and glutathione as reported previously in another animal model of axonal injury and detected multiple metabolites that increased after the injury. After studying the specificity of the identified metabolites to RGCs in histological sections using imaging mass spectrometry, two metabolites, i.e., L-acetylcarnitine and phosphatidylcholine were increased not only preceding the peak of RGC death in the whole retina but also at the RGC layer (2.3-fold and 1.2-fold, respectively). These phospholipids propose novel mechanisms of RGC death and may serve as early biomarkers of axonal injury. The combinatory metabolomics analyses promise to illuminate pathomechanisms, reveal biomarkers, and allow the discovery of new therapeutic targets of glaucoma.

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“…During such crisis, overexpression of PEBP1 has been shown to increase the phosphorylation levels of ERK and Akt pathways, which in turn are known to support the neurogenesis and promote survival by inhibiting the apoptotic pathways. 43,44 These results indicate the possible role of PEBP1 in treatment of glaucoma. 43…”

Section: Pebp1 As Precursor For Hcnp In Neuronsmentioning

confidence: 68%

“…HCNP precursor protein molecules have shown to bind ATP, opioids and phosphatidylethanolamine. 43 Both HCNP and NGF act in accordance to bring about developmental signalling process in cholinergic neurons.…”

Section: Pebp1 As Precursor For Hcnp In Neuronsmentioning

confidence: 99%