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At least 487 records · Page 27Linked to original sources
PubMed1981

Excitation of cardiac sympathetic afferent nerves: effects on renal function.

Cardiac sympathetic afferent nerves can reflexly alter renal efferent nerve activity during myocardial ischemia and in response to mechanical or chemical stimulation of cardiac receptors. They also may influence renal excretion of water and electrolytes; however, this potential influence on renal function has not been determined. Therefore, receptors of cardiac sympathetic afferent nerves were chemically stimulated by epicardial application of bradykinin to determine effects on renal function. Experiments were performed in anesthetized dogs in which cervical vagosympathetic trunks were severed and common carotid arteries were tied to diminish influences of arterial baroreceptors and vagal afferent nerves. Chemical stimulation of cardiac afferent neurons excited renal nerve activity and produced decreases in urine flow rate, glomerular filtration rate, and excretion of sodium and potassium. In contrast, no consistent changes in renal function were observed in control dogs, which did not undergo cardiac afferent stimulation. These data provide evidence that activation of cardiac sympathetic afferent neurons can lead to alterations in excretion of water and electrolytes as well as changes in renal nerve activity.

Afferent Pathways↗
PubMed1988

[Experimental and clinical basis of a method for electrostimulation in spinal cord damage].

In order to assess the advantages of spinal cord electrostimulation at the level below its lesion as a therapeutic intervention restoring motor and autonomic function, experiments were performed in 54 cats with spinal lesions at D11-D12 level. Seven patients with cervical and dorsal lesions were clinically investigated. Both in humans and animals electrostimulation of the spinal cord was applied below the lesioned site all the day round for 30 to 40 days. Early electrostimulation proved effective as a means to recover the motor and autonomic functions, though it had some limitations. In severe lesions of the spinal cord, despite its stimulation, muscular atrophy increased with concomitant decrease in the amplitude of the slow wave electrical activity (SWEA) which was due to spontaneous rhythmical micromovements (SRM). Tissue SRM is essential for the normal functioning of any organ. Thus, interventions stimulating muscular SRM are as necessary as the early electrostimulation.

Adult↗
PubMed2005

Running after the clock.

The way we currently understand vertebrate development is undoubtedly associated with the research undertaken at the "Institut d'Embryologie Cellulaire et Moleculaire" at Nogent-sur-Marne during the last decades. Working in this Institute has been a privilege for many junior and senior researchers. Eight years ago, in this stimulating environment, an exciting observation followed by a series of revealing experiments gave rise to a novel field of research. This study provided evidence for the existence of a molecular clock underlying chick somite formation. In this review, we focus on the cascade of studies that have followed this discovery. Thus far, it has been demonstrated that the molecular clock is operating in several vertebrate models namely chick, mouse, zebrafish, frog and medaka, probably functioning to provide cells with multidimensional positional information. Loss and gain of function experiments and detailed gene promoter analyses have proved very useful in understanding how the clock machinery works. Recent data has also led to the fascinating hypothesis that the clock might not be an exclusive property of somitic cells, but rather a mechanism used by a wide range of embryonic tissues. Meanwhile, the clock "keeps ticking" and many questions are still waiting for an answer.

Animals↗
PubMed2004

TNF receptor type 1 regulates RANK ligand expression by stromal cells and modulates osteoclastogenesis.

TNFalpha is a major osteoclastogenic cytokine and a primary mediator of inflammatory osteoclastogenesis. We have previously shown that this cytokine directly targets osteoclasts and their precursors and that deletion of its type-1 receptor (TNFr1) lessens osteoclastogenesis and impacts RANK signaling molecules. Osteoclastogenesis is primarily a RANK/RANKL-dependent event and occurs in an environment governed by both hematopoietic and mesenchymal compartments. Thus, we reasoned that TNF/TNFr1 may regulate RANKL and possibly RANK expression by stromal cells and osteoclast precursors (OCPs), respectively. RT-PCR experiments reveal that levels of RANKL mRNA in WT stromal cells are increased following treatment with 1,25-VD3 compared to low levels in TNFr1-null cells. Expression levels of OPG, the RANKL decoy protein, were largely unchanged, thus supporting a RANKL/OPG positive ratio favoring WT cells. RANK protein expression by OCPs was lower in TNFr1-null cells despite only subtle differences in mRNA expression in both cell types. Mix and match experiments of different cell populations from the two mice phenotypes show that WT stromal cells significantly, but not entirely, restore osteoclastogenesis by TNFr1-null OCPs. Similar results were obtained when the latter cells were cultured in the presence of exogenous RANKL. Altogether, these findings indicate that in the absence of TNFr1 both cell compartments are impaired. This was further confirmed by gain of function experiments using TNFr1- null cultures of both cell types at which exogenous TNFr1 cDNA was virally expressed. Thus, restoration of TNFr1 expression in OCPs and stromal cells was sufficient to reinstate osteoclastogenesis and provides direct evidence that TNFr1 integrity is required for optimal RANK-mediated osteoclastogenesis.

Animals↗
PubMed2003

Ebf gene function is required for coupling neuronal differentiation and cell cycle exit.

Helix-loop-helix transcription factors of the Ebf/Olf1 family have previously been implicated in the control of neurogenesis in the central nervous system in both Xenopus laevis and the mouse, but their precise roles have remained unclear. We have characterised two family members in the chick, and have performed a functional analysis by gain- and loss-of-function experiments. This study revealed several specific roles for Ebf genes in the spinal cord and hindbrain regions of higher vertebrates, and enabled their precise positioning along the neurogenic cascade. During neurogenesis, cell cycle exit appears to be tightly coupled to migration to the mantle layer and to neuronal differentiation. We show that antagonizing Ebf gene activity allows the uncoupling of these processes. Ebf gene function is necessary to initiate neuronal differentiation and migration toward the mantle layer in neuroepithelial progenitors, but it is not required for cell cycle exit. Ebf genes therefore appear to be master controllers of neuronal differentiation and migration, coupling them to cell cycle exit and earlier steps of neurogenesis. Mutual activation between proneural and Ebf genes suggests that besides their involvement in the engagement of differentiation, Ebf genes may also participate in the stabilisation of the committed state. Finally, gain-of-function data raise the possibility that, in addition to these general roles, Ebf genes may be involved in neuronal subtype specification in particular regions of the CNS.

Animals↗
PubMed2004

The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions.

Embryonic development is tightly controlled. The clustered genes of the Hox family of homeobox proteins play an important part in regulating this development and also proliferation. They specify embryonic structures along the body axis, and are associated with normal and malignant cell growth. The cell-cycle regulator geminin controls replication by binding to the licensing factor Cdt1, and is involved in neural differentiation. Here, we show that murine geminin associates transiently with members of the Hox-repressing polycomb complex, with the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and loss-of-function experiments in the chick neural tube demonstrate that geminin modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb-like activity for geminin. The interaction between geminin and Hox proteins prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional activation of reporter and endogenous downstream target genes, and displaces Cdt1 from its complex with geminin. By establishing competitive regulation, geminin functions as a coordinator of developmental and proliferative control.

Amino Acid Sequence↗
PubMed2006

Antibody blockade of junctional adhesion molecule-A in rabbit corneal endothelial tight junctions produces corneal swelling.

PURPOSE: The ultrastructure of tight junctions in the corneal endothelium has been studied extensively, yet little is known about their molecular composition. Junctional adhesion molecule-A (JAM-A) is a tight junction-associated adhesion protein previously implicated in tight junction assembly and regulation of barrier function. In this study, we sought to investigate the expression and function of JAM-A in the corneal endothelium. METHODS: Immunofluorescence confocal microscopy was used to investigate expression of JAM-A and the related proteins JAM-C, CAR, and AF-6 in the rabbit corneal endothelium. Corneal endothelial perfusion specular microscopy was then used to test the effects of antibodies to JAM-A on corneal swelling. RESULTS: The expression of JAM-A was observed in the tight junctions of rabbit corneal endothelium in a localization pattern identical with that of ZO-1, a known marker of the tight junction and binding partner of JAM-A. Expression of related proteins JAM-C and CAR (Coxsackie and adenovirus receptor) was also observed in the corneal endothelium, but their distribution was diffuse and not limited to the tight junction. Expression of AF-6, a known binding partner of JAM-A, was also observed in the tight junction in a pattern similar to ZO-1. Last, functional experiments were performed in which a monoclonal antibody to JAM-A was shown to increase rabbit corneal swelling by 63% compared with the control. CONCLUSIONS: The results provide new evidence that JAM-A and its binding partner AF-6 are expressed in tight junctions of the corneal endothelium and that JAM-A has a major role in maintaining the corneal endothelial barrier function.

Animals↗
PubMed2002

Effects of anthopleurin-Q on myocardial hypertrophy in rats and physiologic properties of isolated atria in guinea pigs.

AIM: To study effects of anthopleurin-Q (AP-Q) on myocardial hypertrophy in rats and isolated atria in guinea pigs. METHODS: Two myocardial hypertrophy models in rats were established, one introduced by levothyroxine, the other by stenosis of abdominal aorta. Cardiac myocytes morphometry and functional experiments were employed to investigate effects of AP-Q. RESULTS: Low dose of AP-Q (1 microg/kg/d, ip) reduced morphologic changes of myocardial hypertrophy in both rat models. While high dose of AP-Q (10 microg/kg/d, ip) did not, and caused mild hydropic degeneration in cardiomyocytes. High concentration of AP-Q (30 nmol/L) enhanced the contractility, raised automaticity, and prolonged the functional refractory period (FRP) in isolated left atria of guinea pigs; higher concentration (100 nmol/L) triggered arrhythmia in right atria; low concentration of AP-Q (1 nmol/L)did not affect any myocardial properties above. CONCLUSION: Low dose of AP-Q without inotropic effect can hinder the experimental myocardial hypertrophy in rats; high dose with positive inotropic effect may be responsible for its toxic reaction.

Animals↗
PubMed2004

Hedgehog signaling from the ZLI regulates diencephalic regional identity.

The zona limitans intrathalamica (ZLI), a narrow compartment in the vertebrate forebrain that bisects the diencephalon transversely, expresses the secreted factor sonic hedgehog (Shh). Because genetic disruption of Shh in mouse causes severe early developmental defects, this strategy has not been useful in identifying a ZLI-specific role for this gene. To modulate Shh signaling in a spatiotemporally restricted manner, we carried out gain- and loss-of-function experiments in chick embryos using in ovo electroporation and found that Shh signaling is required for region-specific gene expression in thalamus and prethalamus, the major diencephalic brain areas flanking the ZLI. We further show that differential competence of thalamic and prethalamic primordia in responding to Shh signaling is regulated by the transcription factor Irx3. We show that, through the release of Shh, the ZLI functions as a local signaling center that regulates the acquisition of identity for these important diencephalic regions.

Animals↗
PubMed2006

Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: the results of a prospective study.

OBJECTIVE: The cardinal indication for surgical treatment of gallstones is pain attacks. However, following cholecystectomy, 20% of patients remain symptomatic. It is unclear to what extent post-cholecystectomy symptoms can be ascribed to persistence of preoperative symptoms or to new pathology. The pain and digestive pattern in gallstone patients has not been defined in a recent setting with ultrasonography as the diagnostic method. The aim of this study was to characterize a pain pattern that is typical for gallstone disease and to describe the extent of associated dyspepsia. MATERIAL AND METHODS: A total of 220 patients with symptomatic gallstone disease including complicated disease (acute cholecystitis and common bile duct stones) were interviewed using detailed questionnaires to disclose pain patterns and symptoms of indigestion. RESULTS: All patients had pain in the right upper quadrant (RUQ) including the upper midline epigastrium. The pain was localized to the right subcostal area in 20% and to the upper epigastrium in 14%, and in the rest (66%) it was more evenly distributed. An area of maximal pain could be defined in 90%. Maximal pain was located under the costal arch in 51% of patients and in the epigastrium in 41%, but in 3% behind the sternum and in 5% in the back. The pain was referred to the back in 63% of the patients. The mean visual analogue scale (VAS) score was very high: 90 mm on a 0-100 scale. A pattern of incipient or low-grade warning pain with a subsequent relatively steady state until subsiding in the same fashion was present in 90% of the patients. An urge to walk around was experienced by 71%. Pain attacks usually occurred in the late evening or at night (77%), with 85% of the attacks lasting for more than one hour and almost never less than half an hour. Sixty-six percent of the patients were intolerant to at least one kind of food, but only 48% to fatty foods. Symptoms of functional indigestion (gastroesophageal reflux, dyspepsia or irritable bowel symptoms) were seen in the vast majority in association with attacks. CONCLUSIONS: Gallstone-associated pain follows a certain pattern in the majority of patients. The pain is located in a defined area with a point of maximum intensity, is usually referred, and occurs mainly at night with duration of more than one hour. The majority of patients experience functional indigestion, mainly of the reflux type or dyspepsia.

Acute Disease↗
PubMed1996

cis-regulatory elements responsible for quantitative regulation of the rice seed storage protein glutelin GluA-3 gene.

The 897 bp 5' flanking region of the rice storage protein glutelin gene (GluA-3) was analyzed to define cis-regulatory elements responsible for the seed specific expression by progressive 5' deletions and gain-of-function experiments using a truncated CaMV 35S promoter (-90/+9). These constructs were transcriptionally fused either to the firefly luciferase (LUX) or beta-glucuronidase (GUS) reporter gene and introduced into tobacco. It was shown that a 121 bp sequence between -437 and -317 from the transcriptional start site is important for the quantitative regulation of the GluA-3 gene expression. This region contained at least two functionally different cis-regulatory elements. One acts as a general positive element and the other is involved in a specific negative regulation in non-seed tissues.

Animals↗
PubMed2005

Critical function for ADAM9 in mouse prostate cancer.

ADAM9 is a membrane-anchored metalloprotease that is markedly up-regulated in several human carcinomas. Here, we show that ADAM9 is similarly up-regulated in mouse models for prostate, breast, and intestinal carcinoma. To assess whether ADAM9 is critical for the pathogenesis of prostate carcinoma, one of the most common cancers in men, we evaluated how loss of ADAM9 affects tumorigenesis in W(10) mice, a mouse model for this disease. In the absence of ADAM9, most tumors in 50-week-old W(10) mice were well differentiated, whereas littermate controls expressing wild-type ADAM9 had predominantly poorly differentiated, and in some cases significantly larger, tumors. Moreover, gain-of-function experiments in which ADAM9 was overexpressed in mouse prostate epithelium resulted in significant abnormalities, including epithelial hyperplasia at 4 to 6 months of age, and prostatic intraepithelial neoplasia after 1 year. A potential underlying mechanism for the role of ADAM9 in prostate cancer emerged from cell-based assays: ADAM9 can cleave and release epidermal growth factor and FGFR2iiib from cells, both of which have pivotal functions in the pathogenesis of this disease. Taken together, these results suggest that ADAM9 contributes to the pathogenesis of prostate cancer and potentially also other carcinomas, raising the possibility that ADAM9 might be a good target for antitumor drugs.

ADAM Proteins↗
PubMed2007

Viral infections activate types I and III interferon genes through a common mechanism.

Viral infections trigger innate immune responses, including the production of type I interferons (IFN-alpha and -beta) and other proinflammatory cytokines. Novel antiviral cytokines IFN-lambda1, IFN-lambda2, and IFN-lambda3 are classified as type III IFNs and have evolved independently of type I IFNs. Type III IFN genes are regulated at the level of transcription and induced by viral infection. Although the regulatory mechanism of type I IFNs is well elucidated, the expression mechanism of IFN-lambdas is not well understood. Here, we analyzed the mechanism by which IFN-lambda gene expression is induced by viral infections. Loss- and gain-of-function experiments revealed the involvement of RIG-I (retinoic acid-inducible gene I), IPS-1, TBK1, and interferon regulatory factor-3, key regulators of the virus-induced activation of type I IFN genes. Consistent with this, a search for the cis-regulatory element of the human ifnlambda1 revealed a cluster of interferon regulatory factor-binding sites and a NF-kappaB-binding site. Functional analysis demonstrated that all of these sites are essential for gene activation by the virus. These results strongly suggest that types I and III IFN genes are regulated by a common mechanism.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Cloning and functional expression of the mouse epithelial sodium channel.

The epithelial sodium channel (ENaC) plays a major role in the transepithelial reabsorption of sodium in the renal cortical collecting duct, distal colon, and lung. ENaCs are formed by three structurally related subunits, termed alpha-, beta-, and gammaENaC. We previously isolated and sequenced cDNAs encoding a portion of mouse alpha-, beta-, and gammaENaC (alpha-, beta-, and gammamENaC). These cDNAs were used to screen an oligo-dT-primed mouse kidney cDNA library. Full-length betamENaC and partial-length alpha- and gammamENaC clones were isolated. Full-length alpha- and gammamENaC cDNAs were subsequently obtained by 5'-rapid amplification of cDNA ends (5'-RACE) PCR. Injection of mouse alpha-, beta-, and gammaENaC cRNAs into Xenopus oocytes led to expression of amiloride-sensitive (K(i) = 103 nM), Na(+)-selective currents with a single-channel conductance of 4.7 pS. Northern blots revealed that alpha-, beta-, and gammamENaC were expressed in lung and kidney. Interestingly, alphamENaC was detected in liver, although transcript sizes of 9.8 kb and 3.1 kb differed in size from the 3.2-kb message observed in other tissues. A partial cDNA clone was isolated from mouse liver by 5'-RACE PCR. Its sequence was found to be nearly identical to alphamENaC. To begin to identify regions within alphamENaC that might be important in assembly of the native heteroligomeric channel, a series of functional experiments were performed using a construct of alphamENaC encoding the predicted cytoplasmic NH(2) terminus. Coinjection of wild-type alpha-, beta-, and gammamENaC with the intracellular NH(2) terminus of alphamENaC abolished amiloride-sensitive currents in Xenopus oocytes, suggesting that the NH(2) terminus of alphamENaC is involved in subunit assembly, and when present in a 10-fold excess, plays a dominant negative role in functional ENaC expression.

Amino Acid Sequence↗
PubMed1993

Effect of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide on renal function and hemodynamics in the anesthetized rat.

The experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is a nephrotoxicant in the Fischer 344 rat. NDPS induces nephrotoxicity via metabolic bioactivation to one or more metabolites. Both N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (NDHSA), oxidative metabolites of NDPS, are more potent nephrotoxicants than the parent compound. Preliminary studies in our laboratory indicate that altered renal hemodynamics may contribute to the mechanism of NDPS-induced nephrotoxicity. However, it is not known if NDPS affects renal hemodynamics prior to or after altering tubular function. In this study, male Fischer 344 rats (275-300 g) were anesthetized with urethane (1.5 g/kg, i.p.) and prepared for renal function experiments. Renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V) and fraction of GFR excreted as urine (V/GFR) were determined during eight 30 min intervals following NDHS (0.2 or 0.4 mmol/kg, i.p.) or vehicle (sesame oil, 2.5 ml/kg, i.p.) treatment. NDHS (0.2 or 0.4 mmol/kg) decreased GFR while urine flow rate and V/GFR were increased compared to vehicle-treated controls. These alterations in renal function were evident by 2 h post NDHS (0.4 mmol/kg) and by 3 h post-NDHS (0.2 mmol/kg) treatment. RBF of rats receiving NDHS (0.2 or 0.4 mmol/kg) tended to decrease post-NDHS treatment; however, this decrease was not significant. Results of this study indicate that NDHS (0.2 or 0.4 mmol/kg) initially alters renal function by reducing the tubular reabsorption of glomerular filtrate prior to a reduction of GFR and RBF.

Animals↗
PubMed2001

Recognizing one's own face.

We report two studies of facial self-perception using individually tailored, standardized facial photographs of a group of volunteers and their partners. A computerized morphing procedure was used to merge each target face with an unknown control face. In the first set of experiments, a discrimination task revealed a delayed response time for the more extensively morphed self-face stimuli. In a second set of experiments, functional magnetic resonance imaging (fMRI) was used to measure brain activation while subjects viewed morphed versions of either their own or their partner's face, alternating in blocks with presentation of an unknown face. When subjects viewed themselves (minus activation for viewing an unknown face), increased blood oxygenation was detected in right limbic (hippocampal formation, insula, anterior cingulate), left prefrontal cortex and superior temporal cortex. In the partner (versus unknown) experiment, only the right insula was activated. We suggest that a neural network involving the right hemisphere in conjunction with left-sided associative and executive regions underlies the process of visual self-recognition. Together, this combination produces the unique experience of self-awareness.

Adult↗
PubMed2002

Brostallicin, a novel anticancer agent whose activity is enhanced upon binding to glutathione.

Brostallicin (PNU-166196) is a synthetic alpha-bromoacrylic, second-generation DNA minor groove binder structurally related to distamycin A, presently in Phase II trials in Europe and the United States. The compound shows broad antitumor activity in preclinical models and dramatically reduced in vitro myelotoxicity in human hematopoietic progenitor cells compared with that of other minor groove binders. Brostallicin showed a 3-fold higher activity in melphalan-resistant L1210 murine leukemia cells than in the parental line (IC(50) = 0.46 and 1.45 ng/ml, respectively) under conditions in which the cytotoxicity of conventional antitumor agents was either unaffected or reduced. This melphalan-resistant cell line has increased levels of glutathione (GSH) in comparison with the parental cells. Conversely, GSH depletion by buthionine sulfoximine in a human ovarian carcinoma cell line (A2780) significantly decreased both the cytotoxic and the proapoptotic effects of brostallicin. In one experiment, human glutathione S-transferase pi (GST-pi) cDNA was transfected into A2780 cells, and four clones of A2780 with different expression levels of GST-pi were generated (i.e., two clones with high and two clones with low GST-pi expression). A 2-3-fold increase in GST-pi levels resulted in a 2-3-fold increase in cytotoxic activity of brostallicin. Similar results were obtained for GST-pi-transfected human breast carcinoma cells (MCF-7). Brostallicin showed 5.8-fold increased cytotoxicity in GST-pi-transfected versus empty vector-transfected cells with low GST-pi expression. In an in vivo experiment, A2780 clones were implanted into nude mice. The antitumor activity of brostallicin was higher in the GST-pi-overexpressing tumors without increased toxicity. Regarding the mechanism of action, brostallicin interacts reversibly with the DNA minor groove TA-rich sequences but appears unreactive in classical in vitro DNA alkylation assays. We speculated that an intracellular reactive nucleophilic species, e.g., GSH, could react with the alpha-bromoacrylamide moiety functions. Experiments on the interaction with plasmid DNA showed a change of the DNA topology from supercoiled to circular form (nicking) in the presence of GSH, whereas no change was found in its absence. In vitro incubations of brostallicin were performed with the human recombinant GST isoenzymes A1-1, M1-1, and P1-1 (alpha, mu and pi isoenzymes, respectively) in the presence of GSH. The decrease in brostallicin levels was monitored in these incubations; the rate of loss (and therefore brostallicin metabolism) was significantly higher for the M1-1 and P1-1 isoenzymes than for the A1-1 isoenzyme.

Animals↗
PubMed2005

Functional relevance of ceruloplasmin mutations in Parkinson's disease.

Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo-ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)-linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo-ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.

Alleles↗