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PubMed1995

Inability of an isogenic urease-negative mutant stain of Helicobacter mustelae to colonize the ferret stomach.

Eight ferrets specific-pathogen-free for Helicobacter mustelae were given, per dose, approximately 3.0 x 10(7) CFU of either the wild-type parent strain of H. mustelae (NCTC 12032) (two ferrets) the isogenic urease-negative mutant strain of H. mustelae (10::Tn3Km) (four ferrets), or sterile culture broth (two ferrets). Infection status was monitored by endoscopic gastric biopsy for urease activity, histopathology, and culture and by serology at 3, 6, 10, and 21 weeks. All ferrets were necropsied at 25 weeks. Both negative control ferrets remained uninfected, both ferrets receiving the H. mustelae wild-type parent strain became infected after two doses of the organism, and all four ferrets given two doses of the isogenic urease-negative mutant strain of H. mustelae remained uninfected throughout the 6-month study. Histopathology correlated with infection status. H. mustelae-infected ferrets exhibited diffuse mononuclear inflammation in the subglandular region and the lamina propria of the gastric mucosa, while uninfected ferrets showed no or minimal inflammation. These results suggest that urease activity is essential for colonization of the ferret stomach by H. mustelae.

Animals↗

PubMed2003

AFLP marker polymorphism in cucumber (Cucumis sativus L.) near isogenic lines differing in sex expression.

The AFLP technique was used to evaluate the level of polymorphism between two pairs of isogenic cucumber (Cucumis sativus L.) lines (NIL) differing in flower sex expression. The BSA techniques were also applied to find molecular markers linked to sex determination genes (dominant alleles) in those cucumber lines. Sex determination in cucumber is controlled by three main loci F, M and Gy. The interaction of these loci is responsible for the formation of the various phenotypes of flowers in respect to sex in the analyzed lines [corrected]. A female line 2gg with a ff/MM/gygy genotype, isogenic to a monoecious line B10 (genotype ff/MM/GyGy), and a female line Gy3 with a FF/MM/GyGy genotype, isogenic to a hermaphroditic line HGy3 (genotype FF/mm/GyGy). Using 56 combinations of AFLP primers, used for the analysis of lines 2gg and B10, gave 3794 bands, of which 155 (4.1%) were polymorphic. Ten bands distinguished gynoecious and monoecious bulks appearing at the same time in the appropriate parent; they are believed to be linked to the Gy locus. The isogenic lines Gy3 and HGy3 showed a higher level of polymorphism (14.2%). In this case, 55 combinations of primers gave 2996 reaction products, of which 430 showed variation. Twenty bands occurred in one bulk and in one parent, so they are probably associated with the M locus. Using the AFLP technique, the isogenicity of the lines was evaluated. The level of polymorphism (per pair of primer) between lines 2gg and B10 is 0.072% and is four times lower than that between the Gy3 and HGy3 lines (0.27%). The differences in the isogenicity of the lines can result from the degree of their relatedness, which may reflect the way they were derived.

Cucumis sativus↗

PubMed1983

Isolation and characterization of a new type of Escherichia coli K12 phoB mutants.

A new type of Escherichia coli K12 phoB mutant was isolated as 5-fluorouracil-plus-adenosine-resistant derivatives of a upp phoS,T strain. Such phoB mutants (called type III) differ from previously described phoB mutants (types I and II) in the synthesis pattern of phosphate-regulated periplasmic proteins P4a and 30.5 K, sensitivity to toxic compounds, and several other phenotypic characters. The analysis of isogenic strains carrying phoB mutations (type I, II or III) showed that; the phoB gene product exerted (i) a positive control over the synthesis of periplasmic proteins 30.5 K, 11.5 K, and 9 K, inner membrane proteins 32 K and 17.5 K, and outer membrane protein Tsx, (ii) and a direct or indirect negative control over the synthesis of a 20 K phosphate-inducible periplasmic protein.

Adenosine↗

PubMed2026

Exercise elicits mitonuclear protein imbalance and UPRmt in the liver of mice with obesity.

Mitochondrial dysfunction plays a critical role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). It has been proposed that mitochondrial unfolded-protein response (UPRmt) activation improves mitochondrial function in the liver. Growing evidence demonstrates that physical exercise effectively prevents and treats MASLD. However, the effects of exercise on UPRmt activation in the liver are unknown. Thus, we investigated the impact of aerobic training on the mechanisms involved in mitochondrial quality control in the liver in a mouse model of obesity. Liver transcript data from a genetic reference panel of BXD isogenic mice revealed a negative correlation between UPRmt-related genes and hepatic triacylglycerol content. In addition, the liver UPRmt markers were strongly associated with several mitochondrial-related genes in the hepatic tissue of BXD mice and humans. Notably, 4 weeks of aerobic exercise strongly impacted the liver metabolism, preventing intrahepatic lipid accumulation in HFD-fed mice. Physical exercise boosted the NAD-biosynthesis pathway, elicited the mitonuclear protein imbalance, stimulated the protein content of UPRmt-markers, including CLpP, Lonp1, and Yme1L1, and improved the mitochondrial proteostasis and function in the liver in HFD-fed mice. Thus, our findings link the mitonuclear protein imbalance and UPRmt activation in the liver to mitochondrial proteostasis and MASLD prevention in response to physical exercise.

Animals↗

PubMed2005

Different properties of SV channels in root vacuoles from near isogenic Al-tolerant and Al-sensitive wheat cultivars.

Patch-clamp experiments revealed that near isogenic ET8 (Al-tolerant) and ES8 (Al-sensitive) wheat cultivars differed significantly in slow vacuolar channel properties. Under control conditions, whole vacuole currents displayed faster deactivation in ES8. Application of 1.4 microM vacuolar Al3+ caused a 20 mV increase in the activation threshold and slowed activation kinetics in ET8 but not in ES8. Channel density was about 30% higher in ES8 than ET8, and was not altered by 24 h aluminium pre-treatment. However, the activation threshold was reduced in Al-pre-treated ES8. Overall, our data suggests that Alt1 locus may control more than the plasma membrane malate channel in wheat.

Aluminum↗

PubMed2003

Differences between graft product and donor side effects following bone marrow or stem cell donation.

We report graft product stem cell yields and donor safety results of a randomized multicenter study comparing allogeneic peripheral blood stem cell (PBSC) PBSC transplantation with BM transplantation. Matched HLA-identical sibling donors (n=329) were randomized to filgrastim-mobilized PBSC or bone marrow (BM) donation groups. Median yields per kg recipient weight of CD34(+) cells, T cells, and natural killer (NK) cells, respectively, were approximately two-fold, eight-fold, and greater than eight-fold in the PBSC group than in the BM group (CD34(+) cells, 5.8 x 10(6)/kg vs 2.7 x 10(6)/kg; T cells, 300.1 x 10(6)/kg vs 35.7 x 10(6)/kg; NK cells, 28.2 x 10(6)/kg vs 3.6 x 10(6)/kg; P<0.001 for each). In connection with the cell collection procedures, PBSC donors spent a shorter median time in hospital than BM donors (0 vs 2 days; median difference -2 days, 95% CI -2 to 2) and had fewer median days of restricted activity (2 vs 6 days; median difference -3 days, 95% CI -4 to 2). Overall, 65% of PBSC donors and 57% of BM donors reported at least one adverse event (AE), most of which were transient, mild-moderate in severity, and without clinical sequelae. PBSC donors experienced predominantly filgrastim-related AEs, while BM donors experienced predominantly harvest-related AEs.

Adolescent↗

PubMed1999

Time to flowering in brown midrib mutants of maize: an alternative approach to the analysis of developmental traits.

The brown midrib (bm) mutations of maize affect the biosynthesis of lignin, resulting in reddish-brown vascular tissue in the stem, the leaf blade and sheath. Investigating the effects of the change in lignin content and composition on other phenotypic traits in bm mutants is important in increasing the understanding of how secondary metabolism affects plant development. We examined the time to flowering of inbred A619 and near-isogenic lines of bm2, bm1-bm2 and a segregating population with wild-type and bm1 heterozygotes in a controlled experimental design (Latin square) in two locations. Survival analysis was used to describe the distribution of the time to flowering and compare differences between genotypic classes. Survival analysis is a readily accessible technique that can improve inferences in cases where distributions are skewed, or where data are missing or incomplete. The basic approach to survival analysis as well as its specific application to these data is described. After controlling for the effects of the locations, the time to flowering of the bm2 and segregating populations was found to be significantly different from the wild-type and bm1-bm2 populations.

Models, Biological↗

PubMed2005

Evolution of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae.

The shikimate pathway resulting in three aromatic amino acids is initiated in different organisms by two and three 3-deoxy-d-arabino-heptulosonate-7-phosphate synthases, respectively. Aro3p and Aro4p are the yeast enzymes feedback-inhibited by phenylalanine and tyrosine, respectively. A yeast strain deficient in the general control transcriptional regulatory system of amino acid biosynthesis is unable to live in the presence of high amounts of phenylalanine and tyrosine. Here, we show that this yeast strain can be rescued by the expression of aroH from Escherichia coli encoding the tryptophan-regulated AroH as third isoenzyme. Yeast carrying Ec AroH as the only enzyme for the initial step of the shikimate pathway can grow in the absence of tryptophan. Without aromatic amino acids, this yeast strain survives only when the yeast ARO3 promoter instead of the ARO4 promoter drives E. coli aroH. The detailed analysis of Aro3p and Aro4p revealed a triple feedback control by tyrosine/phenylalanine and tryptophan. Dissecting this control allowed engineering of Aro4p S195A as an enzyme, which is inhibited like AroH only by tryptophan. In addition, Aro4p variants were constructed that show an equally strong inhibition by tyrosine and tryptophan (Aro4p P165G Q302R) and in which the regulation by tyrosine and tryptophan was reversed (Aro4p P165G). Our data suggest that yeast possesses only two instead of three isogenes encoding 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases because both isoenzymes can be fine tuned by tryptophan as additional effector and because transcriptional regulation by the general control system can be induced as backup when aromatic amino acids in the environment are imbalanced.

3-Deoxy-7-Phosphoheptulonate Synthase↗

PubMed1978

Coordination of levels of elongation factors Tu, Ts, and G, and ribosomal protein SI in Escherichia coli.

The amounts of the polypeptide chain elongation factors Tu, Ts, and G, and ribosomal protein SI were assessed under various growth conditions using three independent procedures: (a) Immunoprecipitation and gel electrophoresis, (b) radioimmune assay, and (c) activity measurements. It was demonstrated that, during balanced growth of E. coli, the intracellular levels of these proteins increased in proportion to the growth rate, and the ratio of EF-Tu:EF-Ts:EF-G:protein SI was 4-5:1:1:1, at all growth rates. The effects of isoleucine starvation on the rates of synthesis of these proteins were examined using a pair of isogenic stringent and relaxed strains. The syntheses of all these proteins were found to be under the influence of stringent control. These results indicate that in E. coli the syntheses of the above four proteins are regulated in a coordinated manner and are subject to stringent control.

Escherichia coli↗

PubMed1976

Discussion paper: protective immunity in leukemic mice treated with specific "immunogenic" RNA.

Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.

Animals↗

PubMed1993

Characterization and transcriptional regulation of the 2'-N-acetyltransferase gene from Providencia stuartii.

We have cloned the chromosomally encoded 2'-N-acetyltransferase gene [aac(2')-Ia] from Providencia stuartii. DNA sequence analysis of the cloned insert identified a single open reading frame, which is capable of encoding a protein with a predicted molecular mass of 20,073 Da. The deduced AAC(2')-Ia protein showed no significant homology to other proteins, including all of the AAC(3) and AAC(6') proteins. Primer extension analysis was used to identify the aac(2')-Ia promoter, which contained an unusual sequence (CTTTTT) at the -35 region. Expression of the aac(2')-Ia gene occurs at low levels in wild-type P. stuartii strains; therefore, they are aminoglycoside susceptible. We have isolated mutants with high-level AAC(2')-Ia expression at a frequency of 4.8 x 10(-6). Detailed analysis of one mutant demonstrated a 12.2-fold increase in the accumulation of aac(2')-Ia mRNA. In addition, the levels of beta-galactosidase expression from a plasmid-encoded aac(2')-lacZ transcriptional fusion were increased 11.5-fold in this mutant relative to those in an isogenic wild-type strain. These results suggested that a trans-acting factor, designated aar (for aminoglycoside acetyltransferase regulator), controls AAC(2')-Ia expression in P. stuartii.

Acetyltransferases↗

PubMed2020

Metabolic Dysregulation of the Lysophospholipid/Autotaxin Axis in the Chromosome 9p21 Gene SNP rs10757274.

BACKGROUND: Common chromosome 9p21 single nucleotide polymorphisms (SNPs) increase coronary heart disease risk, independent of traditional lipid risk factors. However, lipids comprise large numbers of structurally related molecules not measured in traditional risk measurements, and many have inflammatory bioactivities. Here, we applied lipidomic and genomic approaches to 3 model systems to characterize lipid metabolic changes in common Chr9p21 SNPs, which confer ≈30% elevated coronary heart disease risk associated with altered expression of ANRIL, a long ncRNA. METHODS: Untargeted and targeted lipidomics was applied to plasma from NPHSII (Northwick Park Heart Study II) homozygotes for AA or GG in rs10757274, followed by correlation and network analysis. To identify candidate genes, transcriptomic data from shRNA downregulation of ANRIL in HEK-293 cells was mined. Transcriptional data from vascular smooth muscle cells differentiated from induced pluripotent stem cells of individuals with/without Chr9p21 risk, nonrisk alleles, and corresponding knockout isogenic lines were next examined. Last, an in-silico analysis of miRNAs was conducted to identify how ANRIL might control lysoPL (lysophosphospholipid)/lysoPA (lysophosphatidic acid) genes. RESULTS: Elevated risk GG correlated with reduced lysoPLs, lysoPA, and ATX (autotaxin). Five other risk SNPs did not show this phenotype. LysoPL-lysoPA interconversion was uncoupled from ATX in GG plasma, suggesting metabolic dysregulation. Significantly altered expression of several lysoPL/lysoPA metabolizing enzymes was found in HEK cells lacking ANRIL. In the vascular smooth muscle cells data set, the presence of risk alleles associated with altered expression of several lysoPL/lysoPA enzymes. Deletion of the risk locus reversed the expression of several lysoPL/lysoPA genes to nonrisk haplotype levels. Genes that were altered across both cell data sets were DGKA, MBOAT2, PLPP1, and LPL. The in-silico analysis identified 4 ANRIL-regulated miRNAs that control lysoPL genes as miR-186-3p, miR-34a-3p, miR-122-5p, and miR-34a-5p. CONCLUSIONS: A Chr9p21 risk SNP associates with complex alterations in immune-bioactive phospholipids and their metabolism. Lipid metabolites and genomic pathways associated with coronary heart disease pathogenesis in Chr9p21 and ANRIL-associated disease are demonstrated.

Chromosomes, Human, Pair 9↗

PubMed1977

Histomorphologic evaluation of scleral grafts in experimental bony defects.

This study was undertaken in order to evaluate and compare the effectiveness and fate of the nonautogenous scleral graft in relation to similar grafts of bone marrow and epithelium-free connective tissue grafts from the palate. One hundred round osseous defects 2 mm in diameter, were surgically created in the calveria of 25 rats. Three defects in each animal were filled with the various graft materials obtained from isogenic rats sacrificed at the time of preparation of the bony defects. The fourth defect was left empty as a control. The animals were sacrificed at varying periods of time up to 150 days. Histomorphologic evaluation of the graft sites demonstrated the following: (a) Scleral grafts had effected a functionally adequate repair, without apparent histopathologic changes. (b) Fresh bone marrow provided the greatest osteogenic activity when used as a graft implant. The sclera had an insignificant osteogenic activity when used as a graft implant. The sclera had an insignificant osteogenic potential. (c) Epithelium-free connective tissue was the least effective, both as an osteogenic or functionally adequate graft.

Animals↗

PubMed2001

RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

Alkyl and Aryl Transferases↗

PubMed2003

Role of p53 in regulating constitutive and X-radiation-inducible CD95 expression and function in carcinoma cells.

The p53 tumor suppressor protein is known to regulate the expression of the CD95 (Fas/APO-1) death receptor in a small subset of normal cell types as well as in many cancer cell types. However, whether p53-dependent regulation of CD95 expression is consistently associated with increased susceptibility to CD95-mediated cell death is poorly understood. To address this issue, we examined constitutive and induced CD95 surface expression and function in wild-type p53-expressing carcinoma cells relative to their isogenic p53-inactivated counterparts. We compared HCT116 colorectal carcinoma cells with their p53 biallelic knock-outs and control-transfected MCF-7 breast carcinoma cells with MCF-7 cells expressing a miniprotein inhibitor of p53 (p53DD). In both cell lines, the constitutive expression of surface CD95 was significantly reduced in p53-inactivated cells, as was the apoptotic response to agonistic anti-CD95 antibody. In both cell lines, only cells with wild-type p53 activity exhibited up-regulation of surface CD95 after ionizing irradiation. Interestingly, induction of CD95 expression substantially enhanced the apoptotic response to CD95 ligation only in MCF-7 cells but not in HCT116 cells. These findings provide direct evidence for a major role for wild-type p53 activity in regulating constitutive expression and function of CD95 in carcinoma cells; however, they also demonstrate that the functional effect of DNA damage-induced up-regulation of CD95 may be cell type specific.

Apoptosis↗

PubMed2006

Strict control of telomerase activation using Cre-mediated inversion.

BACKGROUND: Human cells appear exquisitely sensitive to the levels of hTERT expression, the telomerase reverse transcriptase. In primary cells that do not express hTERT, telomeres erode with each successive cell division, leading to the eventual loss of telomere DNA, an induction of a telomere DNA damage response, and the onset of cellular senescence or crisis. In some instances, an average of less than one appropriately spliced hTERT transcript per cell appears sufficient to restore telomerase activity and telomere maintenance, and overcome finite replicative capacity. RESULTS: To underscore this sensitivity, we showed that a widely used system of transcriptional induction involving ecdysone (muristerone) led to sufficient expression of hTERT to immortalize human fibroblasts, even in the absence of induction. To permit tightly regulated expression of hTERT, or any other gene of interest, we developed a method of transcriptional control using an invertible expression cassette flanked by antiparallel loxP recombination sites. When introduced into human fibroblasts with the hTERT cDNA positioned in the opposite orientation relative to a constitutively active promoter, no telomerase activity was detected, and the cell population retained a mortal phenotype. Upon inversion of the hTERT cDNA to a transcriptionally competent orientation via the action of Cre recombinase, cells acquired telomerase activity, telomere DNA was replenished, and the population was immortalized. Further, using expression of a fluorescent protein marker, we demonstrated the ability to repeatedly invert specific transcripts between an active and inactive state in an otherwise isogenic cell background. CONCLUSION: This binary expression system thus provides a useful genetic means to strictly regulate the expression of a given gene, or to control the expression of at least two different genes in a mutually exclusive manner.

Cell Line↗

PubMed1998

Alterations in cardiac gene expression during ventricular remodeling following experimental myocardial infarction.

Following myocardial Infarction (MI) the heart undergoes a process of remodeling characterized by considerable hypertrophy of the non-infarcted myocardium. We have recently characterized the molecular basis of key electrophysiologic alterations that may provide insight into the arrhythmogenecity of post-MI remodeled hypertrophied myocardium. To further characterize other key alterations in the pattern of cardiac gene expression in a time-dependent manner, we have measured mRNA and immunoreactive protein levels of selective cardiac genes in the remodeled hypertrophied left-ventricular (LV) myocardium of rats, 3 and 21 days after left-coronary ligation and compared the results with sham-operated rats. RNase protection assay was performed to assess the expression of c-fos, atrial natriuretic factor (ANF), brain natriuretic factor (BNF), alpha2/3 isoform of Na-K ATPase, cardiac alpha/beta isoform of myosin heavy chain (MHC). Compared to the sham group, the expression of c-fos was increased 10-fold (P<0.02) in the MI group on day 3, but unlike other overload hypertrophy models, the expression remained elevated by three-fold on day 21. Similar to other overload models, the ANF and BNF expression increased significantly. No alterations were observed in the expression of cardiac alpha-actin. There was reexpression of the fetal isogene form of MHC and Na-K ATPase after MI. The beta-MHC mRNA levels, the fetal isoform of MHC, returned to basal levels after 21 days. After an initial five-fold decrease the adult isoform of alphaNa-K ATPase, alpha2 Na-K ATPase mRNA, returned to control levels and similar changes were seen in the corresponding protein levels. These findings indicate that during LV remodeling and hypertrophy following MI, there is an upregulation of early response genes and fetal isogene expression. The pattern of activation, however, is distinct from that observed in other overload models, indicating the possible involvement of alternate signal transduction pathways.

Animals↗

PubMed2005

Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors.

Reactive oxygen species (ROS) signal cascades involved in cell growth, cell death, mitogenesis, angiogenesis and carcinogenesis. ROS are produced as a byproduct of oxidative phosphorylation (OXPHOS) in the mitochondria. It is estimated that 2-4% of the oxygen consumed during OXPHOS is converted to ROS. Besides mitochondria, NADPH-oxidase 1 (Nox1) also generates a significant amount of ROS in the cell. In this paper, we tested the hypothesis that mitochondria control Nox 1 redox signaling and the loss of control of this signaling contributes to tumorigenesis. We analyzed Nox1 expression in a mitochondrial gene knockout (rho(0)) cell line and in the isogenic cybrid cell line in which mitochondrial genes were restored by transfer of wild type mitochondria into rho(0) cells. Our study revealed, for the first time, that the inactivation of mitochondrial genes leads to down-regulation of Nox1 and that the transfer of wild type mitochondrial genes restored the Nox1 expression to a level comparable to that in the parental cell line. Consistent with Nox1 down-regulation, we found that rho(0) cells contained low levels of superoxide anion and that superoxide levels reversed to parental levels in cybrid cells when Nox1 expression was restored by transfer of wild type mitochondria. Increasing mitochondrial superoxide levels also increased the expression of Nox1 in parental cells. Confocal microscopy studies revealed that Nox1 localizes in the mitochondria. Nox1 was highly expressed in breast (86%) and ovarian (71%) tumors and that its expression positively correlated with expression of cytochrome C oxidase encoded by mtDNA. Our study, described in this paper demonstrates the existence of cross talk between the mitochondria and NADPH oxidase. Furthermore, our studies suggest that mitochondria control Nox1 redox signaling and the loss of control of this signaling contributes to breast and ovarian tumorigenesis.

Breast Neoplasms↗