Suppression of Extensive Neurofilament Phosphorylation Rescues α-Internexin/Peripherin-Overexpressing PC12 Cells from Neuronal Cell Death

Lee, Wen-Ching; Kan, Daphne; Chen, Yun-Yu; Han, Shan-Kuo; Lu, Kuo‐Shyan; Chien, Chung‐Liang

doi:10.1371/journal.pone.0043883

Cited by 7 publications

(6 citation statements)

References 55 publications

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“…Membranes were then probed with AlexaFluor® 488 goat α-rabbit IgG (1:250) or AlexaFluor® 488 goat α-mouse IgG 1 (1:250) for 1 h at 25 °C and visualized using a Typhoon 9410 Imager (GE Healthcare Life Sciences, Marlborough, MA). Membranes were also probed with mouse α-β-actin (1:5000; Novus Biologicals) [ 51 ] antibodies. All protein bands of interest were normalized to β-actin bands to act as a loading control.…”

Section: Methodsmentioning

confidence: 99%

Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3

et al. 2016

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Leukemia inhibitory factor (LIF) has been shown to protect oligodendrocytes from ischemia by upregulating endogenous antioxidants. The goal of this study was to determine whether LIF protects neurons during stroke by upregulating superoxide dismutase 3 (SOD3). Animals were administered phosphate-buffered saline (PBS) or 125 µg/kg LIF at 6, 24, and 48 h after middle cerebral artery occlusion or sham surgery. Neurons were isolated from rat pups on embryonic day 18 and used between 7 and 15 days in culture. Cells were treated with LIF and/or 10 µM Akt inhibitor IV with PBS and 0.1 % DMSO acting as vehicle controls. Neurons transfected with scrambled or SOD3 small interfering RNA (siRNA) were subjected to 24-h ischemia after PBS or LIF treatment. LIF significantly increased superoxide dismutase activity and SOD3 expression in ipsilateral brain tissue compared to PBS. Following 24-h ischemia, LIF reduced cell death and increased SOD3 messenger RNA (mRNA) in vitro compared to PBS. Adding Akt inhibitor IV with LIF counteracted the decrease in cell death. Partially silencing the expression of SOD3 using siRNA prior to LIF treatment counteracted the protective effect of LIF-alone PBS treatment. These results indicate that LIF protects neurons in vivo and in vitro via upregulation of SOD3.

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Section: Methodsmentioning

confidence: 99%

Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3

et al. 2016

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“…The tails attain additional negative charges through serine phosphorylation which mediates the interaction between neighboring filaments, affects the organization of NF brushes and is considered to increase the lateral extension of sidearms [Martin et al, ]. Phosphorylation of NF‐H side arms also regulates transport of NFs through axons [Ackerley et al, ; Lee et al, ].…”

Section: Neurofilaments Are Specialmentioning

confidence: 99%

Intrinsic Structural Disorder in Cytoskeletal Proteins

et al. 2013

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Cytoskeleton, the internal scaffold of the cell, displays an exceptional combination of stability and dynamics. It is composed of three major filamentous networks, microfilaments (actin filaments), intermediate filaments (neurofilaments), and microtubules. Together, they ensure the physical and structural stability of the cell, whereby also mediating its large-scale structural rearrangements, motility, stress response, division, and internal transport. All three cytoskeletal systems are built upon the same basic design: they have a central repetitive scaffold assembled from folded building elements, surrounded and regulated by accessory regions/proteins that regulate its formation and mediate its countless interactions with its environment, serving to send regulatory signals to and from the cytoskeleton. Here, we elaborate on the idea that the opposing features of stability and dynamics are also manifest in the dichotomy of the structural status of its components, the core being highly structured and the accessory proteins/regions being highly disordered, and are responsible for most of the regulatory (post-translational) input promoting adaptive responses and providing dynamics necessary for each of the cytoskeletal systems. This pattern entails special consequences, in which the manifold functional advantages of structural disorder, most pronounced in regulatory and signaling functions, are all exploited by nature. (MTs), and it provides the internal scaffold (skeleton) of the cell. It can be considered as a very special organelle, which represents a unique combination of stability and dynamics, physical rigidity and flexibility, long-time persistence and rapid, cataclysmic rearrangements. By providing a special microenvironment, the cytoskeleton ensures the physical separation of cellular constituents, thus segregating and directing cellular activities. It bridges molecular (nano-m) and cellular (micro-m) distances and represent the tracks of transport of cellular constituents over large distances. It provides the locomotive force of cell migration, it drives clustering of membrane proteins, drives cell division and the formation of protrusions the cell uses for exploring its environment. Apparently it does it by a combination of a physically rigid but inherently unstable central scaffold and a flexible and rather variable outer layer of accessory proteins/regions. Due to its central importance in cell physiology, the cytoskeleton is involved in many diseases, ranging from cancer to neurodegeneration [Pajkos et al., 2012;Raychaudhuri et al., 2009;Uversky et al., 2008]. Our central theme here is that multifaceted and highly dynamic behavior is enabled by structural disorder in all three major cytoskeletal constituents, also reflecting their increasing complexity from NFs to the actin cytoskeleton (Supporting Information Table S1, Table I). Intermediate filaments (IFs) have three principal components, IF-L(ight), IF-M(edium), and IF-H(igh), all three of which form an extended coiled-coil structures, from which...

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“…Together with other neuronal IF, peripherin constituted a shape‐maintaining IF network in mature neurons. It was reported that peripherin and α‐internexin can self‐assemble or co‐assemble with neurofilament protein subunits to form the filamentous structure before their translocation into the axons [Lee et al, ]. Neurofilament triplet proteins are constructed by the neurofilament light, medium and heavy subunits, all of which shared the same central rod domain with peripherin [Lee et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that peripherin and α‐internexin can self‐assemble or co‐assemble with neurofilament protein subunits to form the filamentous structure before their translocation into the axons [Lee et al, ]. Neurofilament triplet proteins are constructed by the neurofilament light, medium and heavy subunits, all of which shared the same central rod domain with peripherin [Lee et al, ]. Peripherin plays a crucial role in development of nervous system and it can be highly relevant to pathogenesis of neurodegenerative disorder.…”

Section: Discussionmentioning

confidence: 99%

Effects of extremely low frequency magnetic fields on NGF induced neuronal differentiation of PC12 cells

Jung

Kim

Noh

et al. 2014

Bioelectromagnetics

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Extremely low-frequency magnetic fields (ELF-MFs) affect various cellular processes and systems, such as cell proliferation, differentiation and metabolic pathways. The present study investigated ELF-MFs effect on nerve growth factor (NGF) induced neuronal differentiation of PC12 cells using proteomic applications to understand its role in the enhancement of neuronal differentiation. After 50 Hz, 1 mT ELF-MFs 5-day exposure on NGF induced PC12 cells, it was observed to increase neurite length as well as an increase in the number of neurite bearing cells. It was also discovered that there was a decrease in proliferation activity, which is associated with an increase in differentiated cells. Neuronal differentiation related mRNA levels and protein levels were increased in NGF induced PC12 cells. Compared with NGF induced group, ELF-MFs stimulated PC12 cells had different protein expression as measured with two-dimensional electrophoresis (2-DE) gels. Consequently six differentially expressed spots were detected between the 2-DE maps, which were identified by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF LC/MS/MS) as: peripherin, neurosecretory protein nerve growth factor inducible (VGF8a) precursor, dnaK-type molecular chaperone sp72-ps1 (HSP72-psI), low molecular weight (Mr) phosphotyrosine protein phosphatase isoenzyme AcP1 (LMW-PTP/ACP1), Tubulin alpha-1A (TUBA1A) chain, outcome predictor in acute leukemia 1 homolog (OPA1L). The identification of these proteins provides clues to the mechanism of ELF-MFs stimulation on NGF induced PC12 cells that occur during neuronal differentiation and may contribute to the development novel treatments for neurodegenerative diseases.

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Suppression of Extensive Neurofilament Phosphorylation Rescues α-Internexin/Peripherin-Overexpressing PC12 Cells from Neuronal Cell Death

Cited by 7 publications

References 55 publications

Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3

Leukemia Inhibitory Factor Protects Neurons from Ischemic Damage via Upregulation of Superoxide Dismutase 3

Intrinsic Structural Disorder in Cytoskeletal Proteins

Effects of extremely low frequency magnetic fields on NGF induced neuronal differentiation of PC12 cells

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