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Gerd Schmitz

Publications and source records attributed to Gerd Schmitz.

At least 37 records · Page 2Linked to original sources
PubMed2006

Evaluation of a high-content screening fluorescence-based assay analyzing the pharmacological modulation of lipid homeostasis in human macrophages.

BACKGROUND: For understanding cholesterol and phospholipid efflux pathways there is a need for cellular fluorescence-based high-content screens (HCS) to investigated the cholesterol and phospholipid content in human macrophages. METHODS: Making use of fluorescence imaging based on HCS we have developed a tool to evaluate new agents that can act as inducers of cholesterol efflux. The fluorescence assay is based on the different staining patterns of cholesterol-loaded (E-LDL) and deloaded (HDL3) differentiated monocytes by the saturated, fluorescent lipid probe (1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine)-tetramethyl-rhodamin. RESULTS: Morphologic examination and statistical evaluation of the staining pattern such as gray value, threshold area, shape factor and the spot size distribution provides evidence for a significant pattern change when cholesterol enriched and cholesterol depleted differentiated monocytes were imaged.

Cell Membrane↗
PubMed2006

A flow cytometric screening test for detergent-resistant surface antigens in monocytes.

Rafts resemble cholesterol- and glycosphingolipid-enriched, liquid-ordered plasma membrane microdomains, showing resistance to nonionic detergents, and are involved in various cellular processes. In the present study, we have tested surface antigens on resting and lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes for their detergent resistance (i.e. raft-association), by flow cytometry. Constitutive (CD14, CD32, CD55), or LPS-induced (CD81) raft-association, and detergent solubility (i.e. exclusion of rafts) (CD71) of monocyte antigens in the presence of 0.01% Triton X-100 are clearly demonstrated. Flow cytometric detergent insolubility is a powerful tool for rapid screening the raft-association of monocyte antigens in a whole-blood assay.

Antigens, CD↗
PubMed2006

Molecular defects in the ABCA1 pathway affect platelet function.

Platelet function is sensitive to alterations in cholesterol metabolism, and hypercholesterolemia is associated with enhanced platelet reagibility. Atherogenic low-density lipoproteins (LDL), in particular oxidized LDL, activate src-kinase-family-dependent signalling. In contrast, antiatherogenic high-density lipoproteins(HDL) inhibit platelet aggregation and target the phosphatidylinositol phospholipase C (PI-PLC) pathway. Sphingosine 1-phosphate is a major HDL component and may be crucial for downstream reactions of collagen-induced glycoprotein VI signalling and phosphoinositide 3-kinase. The ATP-binding cassette transporter A1 (ABCA1) regulates cell membrane phospholipid and cholesterol homeostasis and their release to lipid-poor apolipoprotein AI to generate prebeta-HDL precursor particles. ABCA1 also interacts with modulators of vesicular trafficking and number and impaired release of dense bodies from platelets. The ABCA1-NH2-terminus-associated Syntaxin-13, a SNARE complex protein, interacts with syntaxin 13-interacting protein (pallidin) whose deficiency leads to impaired platelet granule release from the dense granule Adapter Protein-3 (AP-3)-related pathway. Interestingly, the cholesterol transporter ABCG1 in addition to ABCA1 is another constituent of the AP-3 pathway, and disorders of lysosome-related organelles such as the Hermansky-Pudlack syndrome complex, Chediak-Higashi syndrome and the ceroid lipofuscinoses provide new opportunities to understand AP-3 pathway-related disorders and the irrelation to membrane phospholipid processing. ABCA1 mutations are involved in dysregulated vesicular trafficking from the trans golgi compartment to the plasma membrane, and ABCA1 R1925Q was shown to contribute to Scott syndrome, a phospholipid-processing disorder of missing surface exposure of phosphatidlyserine. The P2Y12 receptor triggers dense granule secretion by downstream effectors including the G-protein-coupled inward rectifier K+ channel-4 (GIRK-4), and we found the sister geneGIRK-3 associated with the ABCA1 protein in macrophages. It is concluded that the presence of ABCA1 and ABCG1 in the AP-3 pathway will have major impact for membrane phospholipid processing and HDL metabolism and their relation to disorders of lysosome-related organelles.

ATP Binding Cassette Transporter 1↗
PubMed2006

Human ATP-binding cassette transporter TaqMan low-density array: analysis of macrophage differentiation and foam cell formation.

BACKGROUND: ATP-binding cassette (ABC) transporters cause various diseases and regulate many physiologic processes, such as lipid homeostasis, iron transport, and immune mechanisms. Several ABC transporters are involved in bile acid, phospholipid, and sterol transport, and their expression is itself controlled by lipids. In addition, ABC proteins mediate drug export in tumor cells and promote the development of multidrug resistance. METHODS: We created an ABC Transporter TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic Card. We used a 2-microL reaction well with 2 ng of sample. To evaluate this method for lipidomic research and to characterize expression patterns of ABC transporters in cells relevant for atherosclerosis research, we monitored mRNA expression in human primary monocytes, in vitro-differentiated macrophages, and cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists T0901317 and 9-cis retinoic acid, mimicking sterol loading. RESULTS: The method enabled simultaneous analysis of 47 human ABC transporters and the reference gene 18S rRNA in 2 replicates of 4 samples per run. CONCLUSIONS: The new system uses only 2 ng of sample and small volumes of reagent, and the precaptured primers and probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low-Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA profiles in human lipid disorders and cancer-related multidrug resistance and to analyze the pharmacologic and metabolic regulation of ABC transporter expression important for drug development in large-scale screening approaches.

ATP-Binding Cassette Transporters↗
PubMed2005

Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis.

Multidrug resistance protein, also referred as P-glycoprotein (P-gp, MDR1; ABCB1) and multidrug resistance-associated protein (MRP) 1 (ABCC1) and 2 (ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that MDR1, MRP1 as well as MRP5 (ABCC5) and MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood-brain barrier (BBB).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Pharmacogenomics of cholesterol-lowering therapy.

The prevention of cardiovascular disease is critically dependent on lipid-lowering therapy, including 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), cholesterol absorption inhibitors, bile acid resins, fibrates, and nicotinic acid. Although these drugs are generally well tolerated, severe adverse effects can occur in a minority of patients. Furthermore, a subset of patients does not respond to cholesterol-lowering therapy with a reduction in coronary heart disease progression. Significant progress has been made in the identification of common DNA sequence variations in genes influencing the pharmacokinetics and pharmacodynamics of statins and in disease-modifying genes relevant for coronary heart disease (CHD). Among the most promising candidate genes for pharmacogenomic analysis of statin therapy are HMG-CoA reductase as a direct target gene and other genes modulating lipid and lipoprotein homeostasis. Based on data from pharmacogenetic trials, a combined analysis of multiple genetic variants in several genes is more likely to give significant results than single gene studies in small cohorts. In the future, pharmacogenomic testing may allow risk stratification of patients to avoid serious side effects and enable clinicians to select lipid-lowering drugs with the highest efficacy resulting in the best response to therapy.

Apolipoproteins E↗
PubMed2005

Identification of a novel deletion in the ABCC6 gene leading to Pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder, characterized by dermal, ocular and cardiovascular lesions. Genetic defects of the ABCC6 (MRP6) transporter are known to cause PXE. OBJECTIVES: The purpose of this study was to identify the genetic background of a PXE patient with a very early onset of the disease and severe systemic involvement. METHODS: Direct sequencing of genomic DNA obtained from peripheral whole blood. RESULTS: Our patient was found to be compound heterozygous with both ABCC6 alleles having genomic deletions. A novel exon 24-25 deletion was identified on one allele, while the frequently observed exon 23-29 deletion was found on the other allele. The novel deletion is 4.68 kb long and was shown to extend from intron 23 to 25. DNA-sequencing of a 2.03 kb fusion fragment revealed the deletion breakpoints within introns 23 and 25 originating in the middle of two Alu-repeats. CONCLUSION: In a patient with severe clinical symptoms, we found two genomic deletions in regions that might be important for function of the ABCC6 transporter. Genomic deletions in ABCC6 may occur more frequently in PXE patients than previously expected and future genetic analysis should focus on these mutations as well.

Adult↗
PubMed2005

Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro.

AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinA1, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin-B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

Crohn Disease↗
PubMed2005

Transcriptional regulatory networks in lipid metabolism control ABCA1 expression.

The ATP-binding cassette transporters, ABCA1 and ABCG1, are major players in mediating cellular efflux of phospholipids and cholesterol to apoA-I containing lipoproteins including prebeta-HDL and alphaHDL and thereby exert important antiatherogenic properties. Although the exact mechanisms how ABC transporters mediate lipid transport are not completely resolved, recent evidence from several laboratories including ours suggests that vesicular transport processes involving different interactive proteins like beta2-syntrophin, alpha1-syntrophin, Lin7, and cdc42 are critically involved in cellular lipid homeostasis controlled by ABCA1 and ABCG1. Besides sterols and fatty acids as known physiological modulators of the LXR/RXR and SREBP pathways, a growing list of natural and synthetic substances and metabolic regulators such as retinoids, PPAR-ligands, hormones, cytokines, and drugs are particularly effective in modulating ABCA1 and ABCG1 gene expression. Although ABCA1 protein amounts are regulated at the level of stability, the majority of potent activating and repressing mechanisms on ABCA1 function directly act on the ABCA1 gene promoter. Among the inducing factors, liver-X-receptors (LXR), retinoic acid receptors (RAR) and peroxisome proliferator-activated receptors (PPARs) along with their coactivators provide an amplification loop for ABCA1 and ABCG1 expression. The ABCA1 promoter is further stimulated by the ubiquitous factor Sp1 and the hypoxia-induced factor 1 (HIF1), which bind to GC-boxes and the E-box, respectively. Shutdown of ABCA1 expression in the absence of sterols or in certain tissues is mediated by corepressor complexes involving unliganded LXR, sterol-regulatory element binding protein 2 (SREBP2), Sp3, and the SCAN-domain protein ZNF202, which also impacts nuclear receptor signaling. Thus, a highly sophisticated transcriptional network controls the balanced expression of ABCA1.

ATP Binding Cassette Transporter 1↗
PubMed2005

The effect of beta-carotene and its derivatives on cytotoxicity, differentiation, proliferative potential and apoptosis on the three human acute leukemia cell lines: U-937, HL-60 and TF-1.

The influence of beta-carotene (BC) and its derivatives on differentiation, proliferation and apoptosis in three human acute leukemia cell lines was studied. We investigated: (i) the cellular uptake of BC, (ii) the cytotoxicity, (iii) the effect on cell cycle progression and/or apoptosis. The dose- and time-dependent pattern of cellular BC uptake in all studied cell lines was seen. We did not observe any cytotoxic effect of BC and ATRA in the chosen concentrations. There was only limited effect of BC on gene expression. The microarrray analysis of U-937 cell line exposed to BC for 72 h showed an increased expression of BAX gene. This finding was confirmed by real-time Q-PCR analysis, and supported by a flow cytometry apoptosis tests. We did not observe any influence of studied components on cellular proliferation. The induction of differentiation after incubation with ATRA in HL-60 cells was noted. The induction of cellular apoptosis by BC was seen in all studied cell lines. We demonstrated that BC used in the concentrations achievable in vivo does not affect the proliferation and differentiation process of the studied leukemic cell lines, but can influence and enhance the apoptosis by modulating the expression of the regulatory genes.

Apoptosis↗
PubMed2005

Different effect of beta-carotene on proliferation of prostate cancer cells.

It was shown that high doses of beta-carotene (>30 microM) decrease proliferation of prostate cancer cells in vitro. However, it is rather doubtful whether such concentration of beta-carotene is really accessible at cellular level. We studied the effect of 3 and 10 microM beta-carotene on proliferation and gene expression in LNCaP and PC-3 prostate cancer cell lines. Beta-carotene--more efficiently absorbed from medium by androgen-sensitive LNCaP cells--increased proliferation of LNCaP cells whereas it had weaker effect on PC-3 cells. Initial global analysis of expression of genes in both cell lines treated with 10 microM beta-carotene (Affymetrix HG-U133A) showed remarkable differences in number of responsive genes. Their recognition allows for conclusion that differences between prostate cancer cell lines in response to beta-carotene treatment are due to various androgen sensitivities of LNCaP and PC-3 cells. Detailed analysis of expression of selected genes in beta-carotene treated LNCaP cells at the level of mRNA and protein indicated that the observed increase of proliferation could have been the result of slight induction of a few genes affecting proliferation (c-myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle control genes (cdk2, RB, E2F-1).

Androgens↗
PubMed2005

Homozygosity for the 168His variant of the minor histocompatibility antigen HA-1 is associated with reduced risk of primary Sjögren's syndrome.

The genes for the human ATP-binding cassette (ABC) transporter ABCA7 and the minor histocompatibility antigen HA-1 are juxtaposed in close proximity on chromosome 19p13.3. The multispan transmembrane protein ABCA7 contains an extracellular domain that is recognized by antisera from patients with Sjögren's syndrome ("Sjögren-epitope"). Recent work from our laboratory demonstrating the involvement of ABCA7 in cellular ceramide and phosphatidylserine export suggests a role for this transporter in programmed cell death. In HA-1, a protein of unknown function, a His/Arg polymorphism (His168Arg), which constitutes the immunologic target for HA-1-specific cytotoxic T cells, has been causatively linked to graft-versus-host disease after allogeneic stem cell transplantation. Because these findings suggest a potential implication of ABCA7 and HA-1 in immune processes, we tested the hypothesis that allelic variants in both genes are associated with autoimmune disorders. We identified a total of 31 exonic single-nucleotide polymorphisms (SNP) in the ABCA7/HA-1 gene complex, nine of which represent non-synonymous nucleotide alterations. Genotypes of ABCA7 and HA-1 SNP were determined in three distinct Caucasian populations of patients with primary Sjögren's syndrome and ethnically matched controls. Comparison of allele frequencies between these groups revealed that the incidence of the HA-1 168His allele is significantly lower in Sjögren's syndrome patients than in controls (p<0.003). In contrast, the frequencies of all ABCA7 allelic variants and additional HA-1 polymorphisms were similar in patients and controls. In cohorts of patients with systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis, no significant differences in the frequencies of ABCA7 and HA-1 allelic variants were observed relative to controls. Our results suggest that the HA-1 168His variant is associated with reduced susceptibility to primary Sjögren's syndrome.

ATP-Binding Cassette Transporters↗
PubMed2005

RANTES gene polymorphisms predict all-cause and cardiac mortality in type 2 diabetes mellitus hemodialysis patients.

INTRODUCTION: Patients with type 2 diabetes (DM2) and end stage renal disease (ESRD) have a dismal survival prognosis, mainly due to cardiovascular events. There is sparse data on genetic predictors. Chemokines and their receptors are important in regulating leukocyte influx and activation in atherosclerosis, and functional polymorphisms in the respective genes are associated with cardiovascular disease risk. METHODS: We enrolled 225 prevalent Caucasian DM2 patients receiving maintenance hemodialysis in 30 centres in Southern Germany (time from dialysis initiation <2.0 years) from August 1999 to January 2000 for prospective study until December 2003. The CX3CR1 T280M, and MCP-1 -2518 and RANTES -403 and -28 promoter and intronic In1.1T/C polymorphisms were assessed by real-time PCR. Primary end point was all-cause mortality (ACM). RESULTS: Patients carrying the RANTES -403A or In1.1C allele had a significantly higher ACM risk (multivariate hazard ratio for -403A, dominant model=1.81 [95% CI: 1.22-2.67], p=0.003), mainly due to cardiac events. Similar data were obtained by haplotype analysis. The other SNPs showed no effect on survival. DISCUSSION: In DM2 patients with ESRD, ACM due to cardiac events is associated with RANTES gene variants that are known to alter the expression of this chemokine important in atherosclerosis. Further study of the role of chemokine and chemokine receptor gene variation in determining vascular end points is needed.

Aged↗
PubMed2005

C-reactive protein as predictor of death in end-stage diabetic nephropathy: role of peripheral arterial disease.

BACKGROUND: Patients with diabetes type 2 receiving dialysis therapy have a poor survival prognosis, mainly due to cardiovascular events. Increased C-reactive protein (CRP) levels, important in atherosclerosis, are associated with an increased risk for cardiovascular events. However, to date no study has shown the predictive value of CRP in relation to peripheral arterial disease stage. METHODS: We enrolled all 445 prevalent patients with diabetic nephropathy receiving maintenance hemodialysis in 30 centers in Southern Germany from August 1999 to January 2000 for prospective study until December 2003. At inclusion, CRP and a complete clinical phenotype, including peripheral arterial disease Fontaine Stage were determined. The primary end point was all-cause mortality. RESULTS: A total of 305 (68.5%) patients died. An increased log CRP at study inclusion was significantly associated with an increase in hazard ratio (HR) by multivariate Cox regression for all-cause (HR = 1.5, P= 0.002) and cardiac death (HR = 1.76, P= 0.02) in the entire collective. This result was applicable only to patients with peripheral arterial disease Fontaine stage IV (N= 190, multivariate HR = 1.75 for all-cause mortality, P= 0.006). Possibly due to inadequate power, we observed only an insignificant trend for CRP as predictor of all-cause death in patients without peripheral arterial disease or with less severe forms of peripheral arterial disease (HR = 1.36, P= 0.08). CONCLUSION: In contrast to patients with peripheral arterial disease stage IV, patients with less severe atherosclerosis and elevated CRP are, if any, at less risk for cardiovascular mortality, possibly due to the difference in extent of affected vasculature and thus activated platelets and coagulation. Before judging the predictive value of CRP for mortality, peripheral vessel status should be determined.

Aged↗
PubMed2005

Immunohistochemical localization of apolipoprotein A-IV in human kidney tissue.

BACKGROUND: Apolipoprotein A-IV (ApoA-IV) is a 46 kD glycoprotein thought to protect against atherosclerosis. It is synthesized primarily in epithelial cells of the small intestine. Elevated plasma concentrations of ApoA-IV in patients with chronic kidney disease suggest that the human kidney is involved in ApoA-IV metabolism. METHODS: To investigate whether the human kidney directly metabolizes ApoA-IV and which kidney tissue compartment is involved therein, ApoA-IV was localized by immunohistochemistry in 28 healthy kidney tissue samples obtained from patients undergoing nephrectomy. ApoA-IV mRNA expression was analyzed by real-time polymerase chain reaction (PCR) to exclude de novo synthesis in the kidney. RESULTS: ApoA-IV immunostaining was detected in proximal and distal tubular cells, capillaries and blood vessels but not inside glomeruli. ApoA-IV was predominantly found in the brush border of proximal tubules and in intracellular granules and various plasma membrane domains of both proximal and distal tubules. mRNA expression analysis revealed that no ApoA-IV was produced in the kidney. CONCLUSION: The immunoreactivity of ApoA-IV observed in kidney tubular cells suggests a direct role of the human kidney in ApoA-IV metabolism. The granular staining pattern probably represents lysosomes degrading ApoA-IV. The additional ApoA-IV localization in distal tubules suggests a rescue function to reabsorb otherwise escaping ApoA-IV in case proximal tubules cannot reabsorb all ApoA-IV. Since no mRNA expression could be detected in any kidney cells, the observed ApoA-IV immunoreactivity represents uptake and not de novo synthesis of ApoA-IV.

Adult↗
PubMed2005

The influence of cold shock proteins on transcription and translation studied in cell-free model systems.

Cold shock proteins (CSPs) form a family of highly conserved bacterial proteins capable of single-stranded nucleic acid binding. They are suggested to act as RNA chaperones during cold shock inhibiting the formation of RNA secondary structures, which are unfavourable for transcription and translation. To test this commonly accepted theory, isolated CSPs from a mesophilic, thermophilic and a hyperthermophilic bacterium (Bacillus subtilis, Bacillus caldolyticus and Thermotoga maritima) were studied in an Escherichia coli based cell free expression system on their capability of enhancing protein expression by reduction of mRNA secondary structures. The E. coli based expression of chloramphenicol acetyltransferase and of H-Ras served as model systems. We observed a concentration-dependent suppression of transcription and translation by the different CSPs which makes the considered addition of CSPs for enhancing the protein expression in in vitro translation systems obsolete. Protein expression was completely inhibited at CSP concentrations present under cold shock conditions. The CSP concentrations necessary for 50% inhibition were lowest (140 microm) for the protein of the hyperthermophilic and increased when the thermophilic (215 microm) or even the mesophilic protein (451 microm) was used. Isolated in vitro transcription under the influence of CSPs showed that the transcriptory effect is independent from the rest of the cell. It could be shown in a control experiment that the inhibition of protein expression can be removed by addition of hepta-2'-desoxy-thymidylate (dT7); a heptanucleotide that competitively binds to CSP. The data are in line with a hypothesis that CSPs act on bulk protein expression not as RNA chaperones but inhibit their transcription and translation by rather unspecific nucleic acid binding.

Bacillus↗
PubMed2005

The microarray expression analysis identifies BAX as a mediator of beta-carotene effects on apoptosis.

Beta-carotene is a ubiquitous compound rich in foods. However, there are conflicting reports regarding its role in carcinogenesis. We performed a microarray expression analysis in normal [human umbilical vein endothelial cells (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937) actively proliferating cells and found evidence that beta-carotene stimulated vital cellular functions in the former and suppressed them in the latter. These differential effects correlated with the expression of the proapoptotic BCL2-associated X protein (BAX), which was downregulated in HUVECs and upregulated in the two neoplastic cell lines. The quantitative expression analysis using real-time polymerase chain reaction largely confirmed the inhibition of B-cell CLL/lymphoma 2 (BCL2) pathway-mediated apoptosis in HUVECs and its activation in melanoma and leukemic cells. The assays for apoptosis, detecting DNA breaks and caspase activation, showed consistent proapoptotic and antiapoptotic effects in U937 and HUVEC lines, respectively. However, beta-carotene-induced expression changes of BAX and other BCL2 pathway genes did not lead to the predicted induction of apoptosis in the A375 cells.

Antioxidants↗