Rat Schwann Cells Research Articles

Neuroprotection and enhancement of remyelination by estradiol and dexamethasone in cocultures of rat DRG neurons and Schwann cells

A simple and reproducible demyelination–remyelination system was developed with cocultures of rat dorsal root ganglia (DRG) neurons and Schwann cells, and the effects of steroid hormones were examined in this system. Addition of forskolin to the cocultures induced demyelination and lower levels of myelin protein P0 expression were seen in immunoblots after eight days of treatment. Removal of forskolin caused remyelination and the amount of P0 expression was partially recovered. States of demyelination and remyelination were further confirmed by morphological examination of myelin internodes, such as incorporation of fluorescently-labeled fatty acid and immunostaining of P0 and myelin associated glycoprotein. Ultrastructural analyses of the cocultures showed the presence of myeloid bodies and peeling of myelin lamellae during the demyelination process. Using this demyelination–remyelination system, regulatory roles of steroid hormones during demyelination and remyelination were studied. Immunoblots of P0 and incorporation of fluorescently-labeled fatty acid demonstrated that treatments of the cocultures with dexamethasone and estradiol not only reduced the extent of demyelination but also enhanced remyelination. These results suggest that steroid hormones have roles as neuroprotective agents against demyelination and augmentative agents for remyelination.

New 3D hyaluronan-based scaffold for in vitro reconstruction of the rat sciatic nerve

Objective: For peripheral nerve regeneration, three-dimensional distribution and growth of cells within the porous scaffold are of clinical significance. The purpose of this study was to test in vitro a novel hyaluronic acid-based tubular conduit (HYAFF-11 biomaterials: 1 × 10 mm) as a nerve guide.Methods: Human fibroblasts, RN22 Schwann cell lines, human umbilical vein endothelial cells and primary nerve cells, obtained from neonatal rat sciatic nerve, were harvested and seeded on HYAFF-11 devices. Histologic (hematoxylin–eosin), immunohistochemical (antibodies to S100, CD31 and Von Willebrand factor) and PCR analyses were performed after 7 and 14 days from cell seeding onto biomaterials. MTT-based (thiazolyl blue) and DELFIA cell proliferation kit tests were performed to observe the biocompatibility of the cells cultured within the biomaterial devices.Results: We concluded that the conduits were not cytotoxic and demonstrated that cultured RN22 Schwann cells and rat Schwann cells grow in vitro on new artificial nerve conduits. We thus inferred that the HYAFF-11 conduit was a suitable biomaterial able to support nerve cell growth in vitro and after 14 days of cultivation, remained circular with a round lumen, maintaining the size and shape of its original architecture. Finally, attachment and proliferation of endothelial cells attested to the feasibility of developing a coculture system to promote in vivo integration of a microvascularized nerve substitute.Discussion: HYAFF-11 pre-seeded with Schwann and endothelial cells has the potential to be an alternative to autografting for the repair of long peripheral nerve defects.

FA2H is responsible for the formation of 2-hydroxy galactolipids in peripheral nervous system myelin

Myelin in the mammalian nervous system has a high concentration of galactolipids [galactosylceramide (GalCer) and sulfatide] with 2-hydroxy fatty acids. We recently reported that fatty acid 2-hydroxylase (FA2H), encoded by the FA2H gene, is the major fatty acid 2-hydroxylase in the mouse brain. In this report, we show that FA2H also plays a major role in the formation of 2-hydroxy galactolipids in the peripheral nervous system. FA2H mRNA and FA2H activity in the neonatal rat sciatic nerve increased rapidly during developmental myelination. The contents of 2-hydroxy fatty acids were approximately 5% of total galactolipid fatty acids at 4 days of age and increased to 60% in GalCer and to 35% in sulfatides at 60 days of age. The chain length of galactolipid fatty acids also increased significantly during myelination. FA2H expression in cultured rat Schwann cells was highly increased in response to dibutyryl cyclic AMP, which stimulates Schwann cell differentiation and upregulates myelin genes, such as UDP-galactose:ceramide galactosyltransferase and protein zero. These observations indicate that FA2H is a myelination-associated gene. FA2H-directed RNA interference (RNAi) by short-hairpin RNA expression resulted in a reduction of cellular 2-hydroxy fatty acids and 2-hydroxy GalCer in D6P2T Schwannoma cells, providing direct evidence that FA2H-dependent fatty acid 2-hydroxylation is required for the formation of 2-hydroxy galactolipids in peripheral nerve myelin. Interestingly, FA2H-directed RNAi enhanced the migration of D6P2T cells, suggesting that, in addition to their structural role in myelin, 2-hydroxy lipids may greatly influence the migratory properties of Schwann cells.

Acetylcholine inhibits cell cycle progression in rat Schwann cells by activation of the M2 receptor subtype

Cultures of Schwann cells from neonatal rat sciatic nerves were treated with acetylcholine agonists and the effects on cell proliferation evaluated. (3)[H]-thymidine incorporation shows that acetylcholine (ACh) receptor agonists inhibit cell proliferation, and FACS analysis demonstrates cell-cycle arrest and accumulation of cells in the G1 phase. The use of arecaidine, a selective agonist of muscarinic M2 receptors reveals that this effect depends mainly on M2 receptor activation. The arecaidine dependent-block in G1 is reversible because removal of arecaidine from the culture medium induces progression to the S phase. The block of the G1-S transition is also characterized by modulation of the expression of several cell-cycle markers. Moreover, treatment with ACh receptor agonist causes both a decrease in the PCNA protein levels in Schwann cell nuclei and an increase in p27 and p53 proteins. Finally, immuno-electron microscopy demonstrates that M2 receptors are expressed by Schwann cells in vivo. These results indicate that ACh, by modulating Schwann cell proliferation through M2 receptor activation, might contribute to their progression to a more differentiated phenotype.

Bovine lactoferrin protects RSC96 Schwann cells from tumor necrosis factor-α–induced growth arrest via extracellular-signal-regulated kinase 1/2

Bovine lactoferrin (bLF) is a member of the transferrin protein family that is abundant in bovine milk. Recent studies have shown that bLF plays roles in the regulation of cell growth. However, the biological function of bLF in the peripheral nervous system is still unclear. In this study, the immortalized rat Schwann cells (RSC96) were exposed to bLF at concentrations ranging from 10 to 800 μg/ml for 48 h and compared with control group. The bromodeoxyuridine BrdU cell viability assay was used to examine the effect of bLF on cell viability of RSC96 Schwann cells. Cell-counting test was used to assay the growth rate of RSC96 cells after exposure to bLF, and immunoblot analysis was used to test the signaling pathway controlled by bLF in the RSC96 cells. It was found that the viability of the RSC96 cells was increased by more than 25% when treated with 50 μg/ml bLF and the cell number of RSC96 cells was increased by more than threefold when treated with 800 μg/ml bLF. Our results showed that bLF could significantly improve viability and number of RSC96 Schwann cells. Also, bLF could significantly increase the phosphorylation state of extracellular-signal regulated kinase 1/2 (ERK1/2) that could be specifically inhibited by PD98059. Furthermore, bLF could not only protect RSC96 cells from tumor necrosis factor-α (TNF-α) –induced growth arrest but could also restore proliferation rate in TNF-α-treated RSC96 cells. In conclusion, bLF plays a crucial role in the proliferation of RSC96 Schwann cells and the protection of RSC96 Schwann cells from TNF-α-induced growth arrest via ERK1/2 protein.

Expression pattern of peptidylarginine deiminase in rat and human Schwann cells

The peptidylarginine deiminase (PAD) family of enzymes are responsible for conversion of protein-bound arginine to citrulline in most tissues of the body and are garnering increased interest for their physiological and pathological roles. Although it has been shown that oligodendrocytes of the CNS express the PAD isoenzyme type 2, nothing is presently known about PAD expression in Schwann cells, the myelinating cells of the PNS. To evaluate PAD expression in the PNS, cultivated rat and human Schwann cells and slices of fetal, juvenile, and normal and regenerated adult sciatic nerves were examined with RT-PCR, Western blot, and immunohistochemical analysis. Samples from cerebellar cultures and skin served as positive controls. One of the principle findings was that cultivated Schwann cells expressed significant levels of mRNA and protein for the PAD isoenzymes 2 and 3. PAD1 and PAD4, however, were not expressed in any types of Schwann cells. Using double immunofluorescence, the majority of PAD2 staining was localized in immature cell stages. Moreover, increased amounts of PAD2, PAD3, and peptidyl-citrulline were also found in human fetal and rat juvenile and regenerated sciatic nerves as compared to similar normal adult specimens. Neuronal and inducible nitric oxide synthases, enzymes that convert free arginine to citrulline, were also expressed in Schwann cells; however, their massive induction by LPS/K(+), was not reflected in an enhanced peptidyl-citrulline immunosignal. These data suggest that, similar to the CNS, citrullination of proteins may also exert a specific role in thecourse of PNS development and repair.

Correction of protein kinase C activity and macrophage migration in peripheral nerve by pioglitazone, peroxisome proliferator activated‐γ‐ligand, in insulin‐deficient diabetic rats

Pioglitazone, one of thiazolidinediones, a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, is known to have beneficial effects on macrovascular complications in diabetes, but the effect on diabetic neuropathy is not well addressed. We demonstrated the expression of PPAR-gamma in Schwann cells and vascular walls in peripheral nerve and then evaluated the effect of pioglitazone treatment for 12 weeks (10 mg/kg/day, orally) on neuropathy in streptozotocin-diabetic rats. At end, pioglitazone treatment improved nerve conduction delay in diabetic rats without affecting the expression of PPAR-gamma. Diabetic rats showed suppressed protein kinase C (PKC) activity of endoneurial membrane fraction with decreased expression of PKC-alpha. These alterations were normalized in the treated group. Enhanced expression of phosphorylated extracellular signal-regulated kinase detected in diabetic rats was inhibited by the treatment. Increased numbers of macrophages positive for ED-1 and 8-hydroxydeoxyguanosine-positive Schwann cells in diabetic rats were also corrected by the treatment. Pioglitazone lowered blood lipid levels of diabetic rats, but blood glucose and nerve sorbitol levels were not affected by the treatment. In conclusion, our study showed that pioglitazone was beneficial for experimental diabetic neuropathy via correction of impaired PKC pathway and proinflammatory process, independent of polyol pathway.

Mutations in FGD4 Encoding the Rho GDP/GTP Exchange Factor FRABIN Cause Autosomal Recessive Charcot-Marie-Tooth Type 4H

Charcot-Marie-Tooth (CMT) disorders are a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies characterized by muscle weakness and wasting, foot and hand deformities, and electrophysiological changes. The CMT4H subtype is an autosomal recessive demyelinating form of CMT that was recently mapped to a 15.8-Mb region at chromosome 12p11.21-q13.11, in two consanguineous families of Mediterranean origin, by homozygosity mapping. We report here the identification of mutations in FGD4, encoding FGD4 or FRABIN (FGD1-related F-actin binding protein), in both families. FRABIN is a GDP/GTP nucleotide exchange factor (GEF), specific to Cdc42, a member of the Rho family of small guanosine triphosphate (GTP)-binding proteins (Rho GTPases). Rho GTPases play a key role in regulating signal-transduction pathways in eukaryotes. In particular, they have a pivotal role in mediating actin cytoskeleton changes during cell migration, morphogenesis, polarization, and division. Consistent with these reported functions, expression of truncated FRABIN mutants in rat primary motoneurons and rat Schwann cells induced significantly fewer microspikes than expression of wild-type FRABIN. To our knowledge, this is the first report of mutations in a Rho GEF protein being involved in CMT.

Absence of relevant effects of 5 mT static magnetic field on morphology, orientation and growth of a rat Schwann cell line in culture.

The aim of this study is to observe possible changes in the morphology, orientation or cell growth of an in vitro cultured Schwann cell line by 24 h exposure to 5 mT static magnetic fields. The magnetic field generator basically consists of a pair of circular coils in a Helmholtz arrangement and enables temperature to be controlled (37+/-0.1 degrees C). We did not find any statistically significant differences in the cell growth rate between control and exposed cells, nor did we observe any differences in cell morphology or orientation.

Progesterone derivatives increase expression of Krox-20 and Sox-10 in rat Schwann cells

Neuroactive steroids, like progesterone (P) and its 5alpha-reduced derivatives dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), are involved in the control of Schwann cell proliferation and in the myelinating program of these cells. Here, we demonstrate that in culture of rat Schwann cells, P and its derivatives also increase expression of Sox-10 and Krox-20 (i.e., two transcription factors with a key role in Schwann cell physiology and in their myelinating program). Data obtained by quantitative RT-PCR analysis show that treatment with P, DHP, or THP increases mRNA levels of Krox-20. This stimulatory effect anticipates that exerted by P and DHP on Sox-10 gene expression. Thus, although the effect on Krox-20 occurs after 1 h, that on Sox-10 reaches a peak after 2 h. A similar pattern of effect is also evident on their protein levels. As evaluated by Western blot analysis, Krox-20 is increased after 3 h of treatment with P, DHP, or THP, whereas P or DHP stimulates the expression of Sox-10 after 6 h of exposure. A computer analysis performed on rat and human promoters of these two transcription factors shows that putative P-responsive elements are present in Krox-20 but not in Sox-10. Interestingly, many putative binding sites for Krox-20 are present in the Sox-10 promoter. The observations reported here, together with the concept that P and its derivatives are able to influence directly the expression of myelin proteins, suggest that these neuroactive steroids might coordinate the Schwann cell-myelinating program utilizing different intracellular pathways.

Schwann cells express IP prostanoid receptors coupled to an elevation in intracellular cyclic AMP

We have shown previously that prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) are each produced in an explant model of peripheral nerve injury. We report that IP prostanoid receptor mRNA and protein are present in primary rat Schwann cells. IP prostanoid receptor stimulation using prostacyclin produced an elevation in intracellular cyclic AMP concentration ([cAMP](i)) in primary Schwann cells. Peak [cAMP](i) was observed between 5-15 min of stimulation followed by a gradual recovery toward basal level. Phosphorylation of cyclic AMP-response element binding protein (CREB) on Ser(133) was also detected after IP prostanoid receptor stimulation and CREB phosphorylation was inhibited completely by the protein kinase A inhibitor, H-89. Intracellular calcium levels were not affected by IP prostanoid receptor stimulation. Unlike forskolin, IP prostanoid receptor stimulation did not significantly augment Schwann cell proliferation in response to growth factor treatment. However, IP prostanoid receptor stimulation increased the number of Schwann cells that were able to generate a calcium transient in response to P2 purinergic receptor activation. These findings suggest that signaling via the IP prostanoid receptor may by relevant to Schwann cell biology in vivo.

Aging Schwann cells in vitro

Schwann cells (SCs) can support the regeneration of lesioned fiber tracts of the peripheral and central nervous system and have been transplanted alone or in combination with synthetic nerve guides. For neuronal tissue engineering purposes, the cells must be isolated from small biopsies and expanded in vitro. In this study we analyze the impact of cell expansion on 9 different cell parameters, comparing short- and long-term cultured rat SCs, which we refer to as ‘young’ and ‘old’ or ‘aged’ cells, respectively. In comparison to young SCs, old SCs doubled the axonal outgrowth from dorsal root ganglion explants and displayed only one-third as much adhesion to the gray and white matter of spinal cord cryosections. In a 3-dimensional extracellular matrix the two cell populations showed very different cellular responses with regard to cell morphology and cell–cell adhesion. Cell proliferation of old SCs was independent of serum components and was not hampered by contact inhibition. In addition, population doubling times were reduced by a factor of almost three compared to those of young SCs. Despite considerable karyotype changes, with an average of 68.7 chromosomes versus 42 in native rat cells, old SCs did not show any increase in telomerase activity and loss of anchorage dependence – characteristics that are typical of tumor cells. The data also provide biological insights into which cell characteristics (proliferation and adhesion, for example) are functionally clustered and either change or remain constant with aging in vitro. Though the data indicate a lack of tumorigenic transformation coupled with increased neurite outgrowth-promoting activity after extensive SC expansion in vitro, thus suggesting better regeneration qualities, we strongly recommend that in vitro aged rat SCs (>11 passages) should not be employed for tissue engineering.

Study of biocompatibility of small intestinal submucosa (SIS) with Schwann cells in vitro

No satisfactory method currently exists for repairing long peripheral nerve defects. Efforts have been made to fabricate bioactive artificial nerve conduits, comprised of a biomaterial pre-seeded with Schwann cells (SCs), which creating a favorable micro-environment for axonal regeneration, to be an alternative to autografting by means of tissue engineering. Small intestinal submucosa (SIS) possesses special biological characteristics and is comprehensively researched for tissue repairing at varied tissues and organs. This study investigated the biocompatibility of SIS with SCs in vitro. Cultured rat SCs were seeded on SIS. Cell morphology was observed by light microscopy, scanning electron microscopy and transmission electron microscope. The viability of SCs was measured by MTT assay. Secretion of NGF-β and BDNF was quantitatively assessed by ELISA, and NGF-β mRNA and BDNF mRNA were semi-quantitatively assessed by RT–PCR. The results indicated that SCs could adhere, migrate and proliferate on the surface of SIS in good condition with productive function of secreting growth factors. SIS has a good biocompatibility with SCs and SIS pre-seeded with SCs has potential to be an alternate candidate of autografting for repairing long peripheral nerve defects.

Human and rat adult Schwann cell cultures: fast and efficient enrichment and highly effective non-viral transfection protocol

We present a fast protocol that can be used to obtain highly purified cultures of proliferating adult human and rat Schwann cells accessible for non-viral transfection methods. The use of enriched genetically modified adult Schwann cells is of interest in the context of autologous cell transplantation within nerve transplants for peripheral nerve repair. Cell preparation from pre-degenerated adult peripheral nerves is described, together with the use of melanocyte growth medium plus forskolin, fibroblast growth factor-2 (FGF-2), pituitary extract and heregulin as a selective, serum-free culture medium and a subsequent cell enrichment step (cold jet). Proliferating adult Schwann cells can be efficiently genetically modified using optimized, non-viral electroporation protocols. The protocol results in Schwann cell cultures that are more than 90-95% pure, and transfection efficiencies vary depending on the initial cell constitution from 20 to 40%. The procedure takes up to 21 d, depending on the length of the pre-degeneration period.

Dichloroacetate causes reversible demyelination in vitro: potential mechanism for its neuropathic effect

Dichloroacetate (DCA) is an investigational drug for genetic mitochondrial diseases whose use has been mitigated by reversible peripheral neuropathy. We investigated the mechanism of DCA neurotoxicity using cultured rat Schwann cells (SCs) and dorsal root ganglia (DRG) neurons. Myelinating SC-DRG neuron co-cultures, isolated SCs and DRG neurons were exposed to 1-20 mm DCA for up to 12 days. In myelinating co-cultures, DCA caused a dose- and exposure-dependent decrease of myelination, as determined by immunolabeling and immunoblotting for myelin basic protein (MBP), protein zero (P0), myelin-associated glycoprotein (MAG) and peripheral myelin protein 22 (PMP22). Partial recovery of myelination occurred following a 10-day washout of DCA. DCA did not affect the steady-state levels of intermediate filament proteins, but promoted the formation of anti-neurofilament antibody reactive whirls. In isolated SC cultures, DCA decreased the expression of P0 and PMP22, while it increased the levels of p75(NTR) (neurotrophin receptor), as compared with non-DCA-treated samples. DCA had modest adverse effects on neuronal and glial cell vitality, as determined by the release of lactate dehydrogenase. These results demonstrate that DCA induces a reversible inhibition of myelin-related proteins that may account, at least in part, for its clinical peripheral neuropathic effects.

Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3: Implication in Wallerian degeneration

Schwann cells play an important role in peripheral nerve regeneration. Upon nerve injury, Schwann cells are activated and produce various proinflammatory cytokines and chemokines, resulting in the recruitment of macrophages and the phagocytosis of myelin debris. However, it is unclear how nerve injury induces Schwann cell activation. Recently, it was reported that necrotic cells induce immune cell activation via toll-like receptors (TLRs). This suggests that the TLRs expressed on Schwann cells may recognize nerve injury by binding to the endogenous ligands secreted by the damaged nerve, thereby inducing Schwann cell activation. To explore such a possibility, we stimulated rat Schwann cells with necrotic neuronal cells (NNC). The stimulation of Schwann cells with NNC induced the expression of various inflammatory mediators, including TNF-α and iNOS. Studies on the NNC-mediated intracellular signaling pathways revealed that p38 and JNK are involved in the NNC-mediated Schwann cell activation. In addition, NNC-induced proinflammatory gene expression was reduced in mouse Schwann cells derived from TLR2 or TLR3 knockout mice. In summary, these results suggest that necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and TLR3, which might be involved in Wallerian degeneration upon peripheral nerve injury.

Expression and Functional State of the Corticosteroid Receptors and 11β-Hydroxysteroid Dehydrogenase Type 2 in Schwann Cells

To investigate the role of steroid receptors in mediating the reported effects of steroids on Schwann cell (SC) myelination and growth, we determined mRNA contents and transcriptional activities of the corticosteroid (glucocorticosteroid and mineralocorticosteroid) receptors (GR and MR) and sex steroid (progesterone, androgen, and estrogen alpha and beta) receptors in rat SC cultured under proliferative (in the presence of insulin and forskolin, which induces a high intracellular cAMP content) and quiescent conditions. We found no or very low expression and activity of the sex steroid receptors, as shown by mRNA concentrations determined with real-time PCR and transcriptional activities using transient expression of reporter plasmids in SC. These data and binding studies in SC lines demonstrated that the levels of the sex steroid receptors were the limiting factors. GR was clearly expressed (approximately 8000 sequences/ng total RNA) and functional. No significant modification in GR mRNA levels was observed, but an increase in transcriptional efficiency was recorded in proliferating cells compared with quiescent cells. MR was also significantly expressed at the mRNA level (approximately 450 sequences/ng total RNA) under the two culture conditions. No MR transcriptional activity was observed in SC, but a low specific binding of aldosterone was detected in SC lines. 11 beta-Hydroxysteroid-dehydrogenase type 2 (HSD2), an enzyme that inactivates glucocorticoids, was strongly expressed and active in quiescent SC, although in proliferating cells, HSD2 exhibited a strong decrease in activity and mRNA concentration. These data support a physiological role for HSD2 regulation of glucocorticosteroid concentrations in nerve SC.

Sex‐dimorphic effects of progesterone and its reduced metabolites on gene expression of myelin proteins by rat Schwann cells

Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)]. We have now considered the effects of P and its derivatives on these and other myelin proteins [i.e., myelin-associated glycoprotein (MAG) and myelin and lymphocyte protein (MAL)] in sex-specific cultures of rat Schwann cells. Gene expression of myelin proteins was assessed by RNase protection assay. Treatment with P or DHP induced a stimulatory effect on P0 mRNA levels in male but not in female Schwann cells. In contrast, treatment with THP increased gene expression of P0 exclusively in female Schwann cells. A similar sex-difference was also evident for other myelin proteins. Indeed, PMP22 expression was stimulated by treatment with P in male cultures, whereas THP induced an increase of mRNA levels in female cultures. Moreover, MAG was stimulated by THP treatment in male cultures only, whereas MAL expression was unaffected by neuroactive steroid treatment in both male and female cultures. In conclusion, the present observations indicate that the effects of neuroactive steroids on myelin proteins are sexually dimorphic. This finding might represent an important background for sex-specific therapies of acquired and inherited peripheral neuropathies.

NAB2 Represses Transcription by Interacting with the CHD4 Subunit of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

Early growth response (EGR) transactivators act as critical regulators of several physiological processes, including peripheral nerve myelination and progression of prostate cancer. The NAB1 and NAB2 (NGFI-A/EGR1-binding protein) transcriptional corepressors directly interact with three EGR family members (Egr1/NGFI-A/zif268, Egr2/Krox20, and Egr3) and repress activation of their target promoters. To understand the molecular mechanisms underlying NAB repression, we found that EGR activity is modulated by at least two repression domains within NAB2, one of which uniquely requires interaction with the CHD4 (chromodomain helicase DNA-binding protein 4) subunit of the NuRD (nucleosome remodeling and deacetylase) chromatin remodeling complex. Both NAB proteins can bind either CHD3 or CHD4, indicating that the interaction is conserved among these two protein families. Furthermore, we show that repression of the endogenous Rad gene by NAB2 involves interaction with CHD4 and demonstrate colocalization of NAB2 and CHD4 on the Rad promoter in myelinating Schwann cells. Finally, we show that interaction with CHD4 is regulated by alternative splicing of the NAB2 mRNA.

Sexually dimorphic effect of progesterone and its reduced metabolites on the gene expression of myelin proteins in rat Schwann cells

Sexually dimorphic effect of progesterone and its reduced metabolites on the gene expression of myelin proteins in rat Schwann cells