Fish oil attenuated dystrophic muscle markers of inflammation via FFA1 and FFA4 in the mdx mouse model of DMD.
In the present study we investigated the involvement of free fatty acid (FFA) receptors in the anti-inflammatory role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in dystrophic muscles, by administering FFA blockers in the mdx mouse model of dystrophy. Mdx mice (3 months-old) were treated with fish oil capsules (FDC Vitamins; 0.4 g EPA and 0.2 g DHA; gavage) alone or concomitant to FFA1 and FFA4 blockers (GW1100 and AH7614; i.p.). C57BL/10 mice (3 months-old) and untreated-mdx mice received mineral oil and were used as controls. After 1 month of treatment, plasma markers of myonecrosis (total and cardiac creatine kinase; CK), the levels of FFA1 and FFA4 and of the markers of inflammation, nuclear transcription factor kappa B (NFkB), tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) were analyzed in the diaphragm muscle and heart by western blot. Fish oil significantly reduced total CK, cardiac CK and the levels of NFkB (diaphragm), and of TNF-α and IL-1β (diaphragm and heart) in mdx. In the dystrophic diaphragm, FFA1 was increased compared to normal. Blockers of FFA1 and FFA4 significantly inhibited the effects of fish oil treatment in both dystrophic muscles. The anti-inflammatory effects of fish oil in dystrophic diaphragm muscle and heart were mediated through FFA1 and FFA4.
No presente estudo investigamos o envolvimento de receptores de ácidos graxos livres (FFA) no efeito anti-inflamatório dos ácidos eicosapentaenoico (EPA) e docosahexaenoico (DHA) em músculos distróficos, administrando bloqueadores de FFA no camundongo mdx, modelo de distrofia. Camundongos mdx (3 meses de idade) foram tratados com cápsulas de óleo de peixe (FDC Vitamins; 0.4 g EPA e 0.2 g DHA; gavagem) ou com cápsulas de óleo de peixe concomitante a bloqueadores de FFA1 e FFA4 (GW1100 e AH7614; i.p.). Camundongos C57BL/10 (3 meses de idade) e camundongos mdx não tratados receberam óleo mineral e serviram de controle. Após 1 mês de tratamento, marcadores plasmáticos de mionecrose (creatina quinase total e cardíaca; CK), os níveis de FFA1 e FFA4 e dos marcadores de inflamação fator de transcrição nuclear kappa B (NFkB, nuclear transcription factor kappa B), fator de necrose tumoral alpha (TNF-α, tumor necrosis factor alpha) e interleucina 1β (IL-1β) foram analisados no músculo diafragma e no coração através de western blot. O óleo de peixe reduziu de forma significativa a CK total, CK cardíaca e os níveis de NFkB (diafragma), TNF-α e IL-1β (diafragma e coração) no mdx. No diafragma distrófico, FFA1 estava aumentado comparado ao normal. Os bloqueadores de FFA1 e FFA4 inibiram de forma significativa os efeitos do tratamento com óleo de peixe em ambos músculos distróficos. Os efeitos anti-inflamatórios do óleo de peixe nos músculos distróficos diafragma e cardíaco foram mediados por FFA1 e FFA4.
Publication Date: 2020-11-03
Journal: Anatomical record (Hoboken, N.J. : 2007)
Effects of restraint stress on the regulation of hippocampal glutamate receptor and inflammation genes in female C57BL/6 and BALB/c mice.
The two strains of inbred mice, BALB/c and C57BL/6, are widely used in pre-clinical psychiatry research due to their differences in stress susceptibility. Gene profiling studies in these strains have implicated the inflammation pathway as the main contributor to these differences. We focused our attention on female mice and tested their response to 5- or 10-day exposure to restraint stress. We examined the stress induced changes in the regulation of 11 inflammatory cytokine genes and 12 glutamate receptor genes in the hippocampus of female BALB/c and C57BL/6 mice using quantitative PCR. Elevated proinflammatory cytokine genes include Tumor Necrosis Factor alpha (TNFa), nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB), Interleukin 1 alpha (IL1a), Interleukin 1 receptor (IL1R), Interleukin 10 receptor alpha subunit (IL10Ra), Interleukin 10 receptor beta subunit (IL10Rb), and tumor necrosis factor (TNF) super family members. Our results show that BALB/c and C57BL/6 mice differ in the genes induced in response to stress exposure and the level of gene regulation change. Our results show that the gene regulation in female BALB/c and C57BL/6 mice differs between strains in the genes regulated and the magnitude of the changes.
Publication Date: 2019-06-14
Journal: Neurobiology of stress
KPNB1-mediated nuclear import is required for motility and inflammatory transcription factor activity in cervical cancer cells.
Karyopherin β1 is a nuclear import protein involved in the transport of proteins containing a nuclear localisation sequence. Elevated Karyopherin β1 expression has been reported in cancer and transformed cells and is essential for cancer cell proliferation and survival. Transcription factors such as NFÄ¸B and AP-1 contain a nuclear localisation sequence and initiate the expression of multiple factors associated with inflammation and cancer cell biology. Our study investigated the effect of inhibiting nuclear import via Karyopherin β1 on cancer cell motility and inflammatory signaling using siRNA and the novel small molecule, Inhibitor of Nuclear Import-43, INI-43. Inhibition of Karyopherin β1 led to reduced migration and invasion of cervical cancer cells. Karyopherin β1 is essential for the translocation of NFÄ¸B into the nucleus as nuclear import inhibition caused its cytoplasmic retention and decreased transcriptional activity. A similar decrease was seen in AP-1 transcriptional activity upon Karyopherin β1 inhibition. Consequently reduced interleukin-6, interleukin-1 beta, tumour necrosis factor alpha and granulocyte macrophage colony stimulating factor expression, target genes of NFkB and AP-1, was observed. Migration studies inhibiting individual transcription factors suggested that INI-43 may affect a combination of signaling events. Our study provides further evidence that inhibiting KPNB1 has anti-cancer effects and shows promise as a chemotherapeutic target.
Publication Date: 2017-04-22
Allelic mutations in noncoding genomic sequences construct novel transcription factor binding sites that promote gene overexpression.
The growth and survival factor hepatocyte growth factor (HGF) is expressed at high levels in multiple myeloma (MM) cells. We report here that elevated HGF transcription in MM was traced to DNA mutations in the promoter alleles of HGF. Sequence analysis revealed a previously undiscovered single-nucleotide polymorphism (SNP) and crucial single-nucleotide variants (SNVs) in the promoters of myeloma cells that produce large amounts of HGF. The allele-specific mutations functionally reassembled wild-type sequences into the motifs that affiliate with endogenous transcription factors NFKB (nuclear factor kappa-B), MZF1 (myeloid zinc finger 1), and NRF-2 (nuclear factor erythroid 2-related factor 2). In vitro, a mutant allele that gained novel NFKB-binding sites directly responded to transcriptional signaling induced by tumor necrosis factor alpha (TNFα) to promote high levels of luciferase reporter. Given the recent discovery by genome-wide sequencing (GWS) of numerous non-coding mutations in myeloma genomes, our data provide evidence that heterogeneous SNVs in the gene regulatory regions may frequently transform wild-type alleles into novel transcription factor binding properties to aberrantly interact with dysregulated transcriptional signals in MM and other cancer cells.
Publication Date: 2015-07-30
Journal: Genes, chromosomes & cancer
Melatonin attenuates the TLR4-mediated inflammatory response through MyD88- and TRIF-dependent signaling pathways in an in vivo model of ovarian cancer.
Toll-like receptors (TLRs) are effector molecules expressed on the surface of ovarian cancer (OC) cells, but the functions of the TLR2/TLR4 signaling pathways in these cells remain unclear. Melatonin (mel) acts as an anti-inflammatory factor and has been reported to modulate TLRs in some aggressive tumor cell types. Therefore, we investigated OC and the effect of long-term mel therapy on the signaling pathways mediated by TLR2 and TLR4 via myeloid differentiation factor 88 (MyD88) and toll-like receptor-associated activator of interferon (TRIF) in an ethanol-preferring rat model.
To induce OC, the left ovary of animals either consuming 10% (v/v) ethanol or not was injected directly under the bursa with a single dose of 100 μg of 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 μL of sesame oil. The right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of mel (200 μg/100 g b.w./day) for 60 days.
Although mel therapy was unable to reduce TLR2 levels, it was able to suppress the OC-associated increase in the levels of the following proteins: TLR4, MyD88, nuclear factor kappa B (NFkB p65), inhibitor of NFkB alpha (IkBα), IkB kinase alpha (IKK-α), TNF receptor-associated factor 6 (TRAF6), TRIF, interferon regulatory factor 3 (IRF3), interferon β (IFN-β), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. In addition, mel significantly attenuated the expression of IkBα, NFkB p65, TRIF and IRF-3, which are involved in TLR4-mediated signaling in OC during ethanol intake.
Collectively, our results suggest that mel attenuates the TLR4-induced MyD88- and TRIF-dependent signaling pathways in ethanol-preferring rats with OC.
Publication Date: 2015-02-07
Journal: BMC cancer
Cytokine polymorphisms are associated with fatigue in adults living with HIV/AIDS.
Fatigue has been associated with inflammation and cytokine activity among adults, but this relationship has not been evaluated among adults living with HIV. Diurnal patterns of fatigue have been previously identified in adults with HIV/AIDS. Thus, the purpose of this study was to describe these fatigue patterns in relation to cytokine plasma concentrations and gene polymorphisms. A convenience sample of 317 adults living with HIV/AIDS completed a measure of fatigue in the morning and evening for three consecutive days; participants reporting low levels of both morning and evening fatigue (n=110) or high levels of fatigue in the morning and evening (n=114) were included in the analysis, resulting in a final sample of 224 adults (151 men, 55 women, and 18 transgender). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB-1 and -2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. Controlling for genomic estimates of ancestry and self-reported race/ethnicity and gender, the high fatigue pattern was associated with five single nucleotide polymorphisms (SNPs): IL1B rs1071676 and rs1143627, IL4 rs2243274, and TNFA rs1800683 and rs1041981. The IL1B and TNFA polymorphisms were not associated with plasma levels of IL-1β or TNFα, respectively. This study strengthens the evidence for an association between inflammation and fatigue. In this chronic illness population, the cytokine polymorphisms associated with high levels of morning and evening fatigue provide direction for future personalized medicine intervention research.
Publication Date: 2014-03-19
Journal: Brain, behavior, and immunity
Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture.
Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011's effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines.
Muscle cell cultures derived from lean, overweight and diabetic-obese subjects were used. Expression of pro-inflammatory genes and inflammatory response of human myotubes were evaluated by real-time polymerase chain reaction (RT-PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays.
We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFα (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in myotubes derived from diabetic-obese subjects as compared with myotubes derived from normal-lean subjects. In line with this, basal Akt phosphorylation (Ser473) was significantly higher, while insulin-stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal-overweight and diabetic-obese subjects compared with normal-lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin-stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine-induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue.
PMI 5011 improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines.
Publication Date: 2014-02-14
Journal: Diabetes, obesity & metabolism
Toll-like receptor 11-initiated innate immune response in male mouse germ cells.
Toxoplasma gondii and uropathogenic Escherichia coli (UPEC) may infect the testis and impair testicular function. Mechanisms underlying testicular innate immune response to these two pathogens remain to be clarified. The present study examined the function of TLR11, which can be recognized by T. gondii-derived profilin and UPEC, in initiating innate immune response in male mouse germ cells. TLR11 is predominantly expressed in spermatids. Profilin and UPEC induced the expressions of different inflammatory cytokine profiles in the germ cells. In particular, profilin induced the expressions of macrophage chemotactic protein 1 (MCP1), interleukin 12 (IL12), and interferon gamma (IFNG) through nuclear factor KB (NFKB) activation. UPEC induced the expressions of MCP1, IL12, and IFNG, as well as tumor necrosis factor alpha (TNFA), IL6, and IFNB, through the activation of NFKB, IFN regulatory factor 3, and mitogen-activated protein kinases. Evidence showed that profilin induced the innate response in male germ cells through TLR11 signaling, and UPEC triggered the response through TLR11 and other TLR-signaling pathways. We also provided evidence that local injection of profilin or UPEC induces the innate immune response in the germ cells. Data describe TLR11-mediated innate immune function of male germ cells in response to T. gondii profilin and UPEC stimulations. This system may play a role in testicular defense against T. gondii and UPEC infections in mice.
Publication Date: 2014-01-10
Journal: Biology of reproduction
Polymorphisms of interleukin-1 Beta and interleukin-17Alpha genes are associated with restless legs syndrome.
Dopamine, iron, and inflammatory pathways are considered important to the development of restless legs syndrome (RLS). Recent genetic studies support involvement of dopamine and iron; however, cytokine gene variation in the inflammatory component remains unexplored. A recent study reported a high prevalence of RLS among HIV-infected adults. We estimate occurrence of RLS in an ethnically diverse sample of HIV-infected adults and examine differences in demographic factors, clinical characteristics, and biomarkers relating to dopamine, iron, and inflammation between adults with and without RLS symptoms.
A prospective longitudinal study aimed at identifying biomarkers of RLS symptom experience among HIV-infected adults.
316 HIV-positive adults were evaluated using International RLS Study Group criteria. Genes were chosen for hypothesized relationships to dopamine (NOS1, NOS2), iron (HFE) or inflammation-mediated by cytokine genes (interferon [IFN], interleukin [IL], nuclear factor kappa-B [NFKB], and tumor necrosis factor alpha [TNFA]).
Similar to general population estimates, 11% of the sample met all four RLS diagnostic criteria. Controlling for race, gender, and hemoglobin, carrying two copies of the minor allele for IL1B rs1143643, rs1143634, or rs1143633 or carrying the minor allele for IL17A rs8193036 was associated with increased likelihood of meeting RLS diagnostic criteria.
This study provides preliminary evidence of a genetic association between IL1B and IL17A genes and RLS.
Publication Date: 2013-03-06
Journal: Biological research for nursing
What blood temperature for an ex vivo extracorporeal circuit?
Ex vivo circuits are commonly used to evaluate biomaterials or devices used for extracorporeal blood purification. However, various aspects of the ex vivo circuit, apart from the circuit materials, may affect inflammation and coagulation. One such aspect is temperature. The aim of this study was to evaluate the influence of different blood temperature conditions on inflammation parameters in an ex vivo circuit. Blood was collected from 20 healthy volunteers and run through three different experimental conditions for 4 h: a miniaturized ex vivo extracorporeal circuit equipped with a blood warmer set to 37°C, the same circuit without the warmer (23°C), and a tube placed in an incubator at 37°C (no circuit). We measured the granulocyte macrophage colony-stimulating factor, the tumor necrosis factor, and the interleukin (IL)-1β, IL-6, IL-8, and IL-10 concentrations at baseline, 15, 60, 120, and 240 min. Human leukocyte antigen (HLA)-DR, CD11b, CD11a, CD62L, tumor necrosis factor alpha converting enzyme, annexin V expression, and NFkB DNA binding were measured in monocytes and polymorphonuclear neutrophils (PMNs) using flow cytometry at baseline, 120 min, and 240 min. While cytokine production over time was very slight at room temperature, levels increased by more than 100-fold in the two heated conditions. Differences in the expression of some surface markers were also observed between the room temperature circuit and the two heated conditions (CD11b PMN, P < 0.0001; HLA-DR Mono, P=0.0019; and CD11a PMN, P<0.0001). Evolution of annexin V expression was also different over time between the three groups (P=0.0178 for monocytes and P=0.0011 for PMNs). A trend for a greater NFkB DNA binding was observed in the heated conditions. Thus, for ex vivo studies using extracorporeal circuits, heating blood to maintain body temperature results in significant activation of inflammatory cells while hypothermia (room temperature) seems to suppress the leukocyte response. Both strategies may lead to erroneous conclusions, possibly masking some specific effects of the device being studied. Investigators in this field must be aware of the fact that blood temperature is a crucial confounding parameter and the type of "background noise" they will face depending on the strategy adopted.
Publication Date: 2011-02-15
Journal: Artificial organs
Osteoclast function, bone turnover and inflammatory cytokines during infective exacerbations of cystic fibrosis.
Raised levels of pro-inflammatory, pro-resorptive cytokines during pulmonary infection may contribute to osteoporosis in cystic fibrosis (CF). We assessed osteoclast number and activity during infective exacerbations and examined their relationship to serum inflammatory cytokines and bone turnover markers.
Serum samples from 24 adults with CF were obtained before, during and after treatment of infection. Osteoclastic cells were generated from peripheral blood mononuclear cells and their number and activity assessed. Serum osteocalcin, type 1 collagen cross-linked N-telopeptide (NTx), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha), receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) were measured.
Osteoclast number and activity were increased at the start of exacerbation and decreased with antibiotic therapy. Significant correlations were demonstrated between osteoclast formation and serum TNFalpha, OPG, osteocalcin and NTx and between osteoclast activity and serum IL-6 and NTx.
The systemic response to infection is associated with increased bone resorptive activity in patients with CF.
Publication Date: 2009-12-17
Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
Updating the effects of fatty acids on skeletal muscle.
In this review we updated the fatty acid (FA) effects on skeletal muscle metabolism. Abnormal FA availability induces insulin resistance and accounts for several of its symptoms and complications. Efforts to understand the pathogenesis of insulin resistance are focused on disordered lipid metabolism and consequently its effect on insulin signaling pathway. We reviewed herein the FA effects on metabolism, signaling, regulation of gene expression and oxidative stress in insulin resistance. The elevated IMTG content has been associated with increased intracellular content of diacylglycerol (DAG), ceramides and long-chain acyl-coenzyme A (LCA-CoA). This condition has been shown to promote insulin resistance by interfering with phosphorylation of proteins of the insulin pathway including insulin receptor substrate-1/2 (IRS), phosphatidylinositol-3-kinase, (PI3-kinase) and protein kinase C. Although the molecular mechanism is not completely understood, elevated reactive oxygen (ROS) and nitrogen species (RNS) are involved in this process. Elevated ROS/RNS activates nuclear factor-kappaB (NFkB), which promotes the transcription of proinflammatory tumoral necrosis factor alpha (TNFalpha), decreasing the insulin response. Therefore, oxidative stress induced by elevated FA availability may constitute one of the major causes of insulin resistance in skeletal muscle.
Publication Date: 2008-06-11
Journal: Journal of cellular physiology
Fructose and the metabolic syndrome: pathophysiology and molecular mechanisms.
Emerging evidence suggests that increased dietary consumption of fructose in Western society may be a potentially important factor in the growing rates of obesity and the metabolic syndrome. This review will discuss fructose-induced perturbations in cell signaling and inflammatory cascades in insulin-sensitive tissues. In particular, the roles of cellular signaling molecules including nuclear factor kappa B (NFkB), tumor necrosis factor alpha (TNF-alpha), c-Jun amino terminal kinase 1 (JNK-1), protein tyrosine phosphatase 1B (PTP-1B), phosphatase and tensin homolog deleted on chromosome ten (PTEN), liver X receptor (LXR), farnesoid X receptor (FXR), and sterol regulatory element-binding protein-1c (SREBP-1c) will be addressed. Considering the prevalence and seriousness of the metabolic syndrome, further research on the underlying molecular mechanisms and preventative and curative strategies is warranted.
Publication Date: 2007-07-04
Journal: Nutrition reviews
Clathrin heavy chain is required for TNF-induced inflammatory signaling.
Tumor necrosis factor receptor I recruits tumor necrosis factor receptor-associated death domain (TRADD) and multiple kinases that ultimately phosphorylate inhibitor kappa B (IKB alpha). Degradation of phospho-IKB alpha (p-IKB alpha) frees nuclear factor kappa B (NFKB) to be active and phosphorylated. Many receptors require clathrin-mediated endocytosis to provide the scaffolds necessary for signaling. Therefore, we investigated the role of clathrin heavy chain (CHC) in tumor necrosis factor alpha (TNF-alpha)-induced IKB alpha phosphorylation and NFKB activation. We hypothesized that CHC was required for TNF-alpha-induced inflammatory signaling.
We treated human pulmonary epithelial cells with small interfering RNA to knock down intracellular CHC (CHCsil). TRADD and scrambled (noncoding) small interfering RNA sequences were used as positive and negative controls, respectively. Treatment groups were exposed to 10 ng/mL of TNF-alpha. Total I kappaB alpha, p-I kappaB alpha, and phosphorylated P65 (a subunit of NFKB) were determined by immunoblot staining. Densitometry was normalized to controls for the analysis of the stains. TNF-alpha-induced release of monocyte chemoattractant protein 1 (MCP-1) was determined by enzyme-linked immunosorbent assay. Statistical analyses were determined by analysis of variance or paired t test as appropriate.
TNF-alpha-induced I kappaB alpha phosphorylation and degradation at 5 and 30 minutes, respectively, and induced P65 phosphorylation. CHCsil diminished p-I kappaB alpha by 91% (P < .03); however, I kappaB alpha degradation was not affected. CHC knockdown caused a 66% decrease in P65 phosphorylation after 3 minutes of TNF-alpha. CHCsil decreased TNF-alpha-induced MCP-1 by 46% (P < .05), compared with control.
CHCsil significantly impairs phosphorylation of both I kappaB alpha and P65. CHCsil also significantly decreased MCP-1 production. These data suggest that CHC is required for certain TNF-alpha-induced, inflammatory signaling pathways.
Publication Date: 2006-08-15
Tumour necrosis factor alpha and interleukin-1 beta induce specific subunits of NFKB to bind the HIV-1 enhancer: characterisation of transcription factors controlling human immunodeficiency virus type 1 gene expression in neural cells.
In human astrocytoma and neuroblastoma cell lines tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) induced NFKB and an additional KB-specific protein of approximately 80 K to bind the HIV-1 enhancer. One nucleoprotein complex contained prototypical NFKB comprising of p50 and p65 subunits and a second contained the p65 subunit and an 80 K factor, p80. Over a 24 hr period of cytokine stimulation the p50/p65 complex of NFKB was present in the nucleus whilst the second complex declined in abundance after two hours due to the decline of p80. In unstimulated cells, DNAse I footprinting revealed a previously unidentified octamer-like binding site in the negative regulatory element (NRE) of the HIV-1 long terminal repeat (LTR) which specifically bound protein factors present in human astrocytoma, neuroblastoma and murine oligodendroglioma cell lines. A second unique motif, also in the NRE, was observed with extracts from one human neuroblastoma cell line and a murine oligodendroglioma. Footprinting analysis also confirmed that Sp1, TATA, Site A and Site B motifs of the LTR were occupied by nuclear factors present in neural cells.
Publication Date: 1994-08-30
Journal: Biochemical and biophysical research communications