Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure

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Changes in neuroendocrine elements in bronchial mucosa in chronic lung disease in adults
(1995) Pilmane, M.; Luts, A.; Sundler, F.; Department of Morphology
Background - It is not clear whether there is any association between metaplasia of the bronchial epithelium and changes in the distribution of neuroendocrine cells. This study examined, by immunohistological techniques, the distribution of neuroendocrine cells and juxtamucoscal nerve fibres in bronchial biopsies showing metaplastic changes. Methods - Bronchial biopsies from 12 subjects with epithelial metaplasia associated with bronchiectasis and diffuse pulmonary fibrosis were examined by conventional light microscopy and immunohistological techniques for protein gene product 9.5 (PGP), chromogranin A and B (CAB), serotonin, vasoactive intestinal peptide (VIP), substance P (SP), calcitonin generelated peptide (CGRP), calcitonin (CT), and gastrin releasing peptide (GRP). Results - Regions of non-metaplastic epithelium contained numerous PGP and serotonin immunoreactive cells. Subpopulations of these cells displayed CAB, CGRP, CT, and GRP immunoreactivity. Metaplastic epithelium contained only a few weakly stained PGP, serotonin, CAB, GRP, CT and CGRP immunoreactive cells in six cases. Metaplastic epithelium was characterised by a high number of CABcontaining cells in six cases and in these biopsies prominent PGP-contaiIiing nerve bundles were seen in the subepithelial layer beneath the metaplastic epithelium. Conclusions - The distribution patterns of neuroendocrine cells and neuronal elements vary between areas of normal and metaplastic epithelium and within areas of metaplastic epithelium. Neuronal hyperplasia was associated with an increase in the number of CAB-containing cells within the metaplastic epithelium.
ENERGY COUPLING SITES IN THE ELECTRON-TRANSPORT CHAIN OF ZYMOMONAS-MOBILIS
(1995-11-01) KALNENIEKS, U; GALININA, N; IRBE, I; TOMA, M
Spectrophotometrical alterations in the support tissue of large bronchi in humans
(1996) Pilmane, Mara; Skidenko, Nagezda; Mironova, Nina; Department of Morphology
We investigated spcctrophotometrically hyaline cartilage of large bronchi in 53 humans. The gradual increase of optical density (OD) both in cytoplasm of chondrocytes (CH) and extracellular matrix (EM) from the proliferative zone to the zone of hypertrophied CH was revealed in the first type of nonchanged cartilage. The second type of non-changed and partly degenerative cartilage exhibited the same distribution of OD along all zones through insignificant changes of OD in the EM. The third type of degenerative and asbestotic cartilage showed cither significant increase or decrease of OD in all zones. We suggest, that the different types of distribution of the OD corresponds to the degeneration of cartilage, but does not depend on age and duration of disease.
Incidence trends in childhood onset IDDM in four countries around the Baltic sea during 1983-1992
(1997) Padaiga, Z.; Tuomilehto, J.; Karvonen, M.; Podar, T.; Brigis, G.; Urbonaite, B.; Kohtamäki, K.; Lounamaa, R.; Tuomilehto-Wolf, E.; Reunanen, A.; Department of Public Health and Epidemiology
We present secular trends of childhood onset insulin-dependent diabetes mellitus (IDDM) in Finland, Estonia, Latvia and Lithuania during the period of 1983-1992. Incidence data were obtained from the national IDDM registries. The average age-standardized incidence per 100,000/year was 35.0 in Finland, followed by 10.2 in Estonia, 7.1 in Lithuania and 6.5 in Latvia. A male excess in incidence was recorded in Finland (1.15) and Latvia (1.01). In all countries, the highest age-specific risk of IDDM was observed in the 11-13 year age range. The large difference in incidence between Finland and other Baltic countries was seen even in 1-2-year-old children. During the 10-year study period overall changes in incidence of IDDM were relatively small in these four countries. The incidence increased in Finland and Lithuania on average by 1% and 1.4% per year, respectively. A statistically significant increase was recorded only in 0-4 year old children in Finland, at 5.6% per year. In Estonia, an 8.3% increase in this age group, however, was not statistically significant The different trends in the age-group specific incidence rates were confirmed in Finland. In conclusion, from 1983 to 1992 the incidence of childhood onset IDDM was increasing in Finland and Lithuania, while in Latvia and Estonia it was stable. There are still great differences in IDDM incidence between the countries around the Baltic Sea.
Experimental Study of Neuropeptide Containing Nerve Fibres
(1997) Paegle, D; Skagers, Andrejs; Pilmane, Māra; Department of Morphology
Anhydrobiosis in yeast: Activation effect
(1997-01) Rapoport, AI; Khroustalyova, GM; Kuklina, EN
Demonstration of collagen type VI and alpha-smooth muscle actin in renal fibrotic injury in man
(1998-02) Groma, Valērija; Rīga Stradiņš University
Background. Overproduction of collagenous fibres types I and III is a common finding of fibrotic injury. Collagen type VI is generally associated with type I. Appearance of fibroblasts expressing alpha-smooth muscle actin (ASMA) and their role in fibrogenesis has been partly defined. However, correlation between renal fibroblasts and accumulation of microfibrillar collagen type VI, as well as its exact distribution, is not fully delineated. This study was undertaken to investigate these issues using a complex morphological approach. Methods. Morphological examination included immunohistochemical detection of the collagen type VI and ASMA, relying on a streptavidin-biotin-peroxidase-based technique, and electron microscopy. Results. Collagen type VI was strongly expressed in areas of fibrotic injury, although mild expression was always revealed in renal interstitium. Glomerular immunoreactivity with the anti-collagen type VI antibody was almost nil excepting cases of diabetic glomerulosclerosis and amyloid nephrosis. Glomerular nodules in cases of diabetes displayed intense reactivity. Mesangial, as well as discontinuous peripheral deposition of collagen along the glomerular basement membrane, was noticed in case of amyloidosis. Ultrastructurally, cross-banded collagen microfibrils were found in renal interstitium in close association with the fibroblast membrane. Moreover, fibrillar elements revealing tubular structure and fine filamentous material were observed between cross-banded microfibrils. Some of fibroblasts exhibited bundles of microfilaments in their cytoplasm. An increased number of ASMA-positive cells was detected in fibrotic interstitium. An intense concentric network made up of actin-bearing cells surrounded glomerular capillaries in the case of crescentic glomerular lesions. Conclusions. Markedly increased deposition of collagen type VI takes place in renal fibrotic lesions. Simultaneously, interstitial fibrotic areas appeared to contain a great number of fibroblasts sharing morphological characteristics of classic fibroblasts and smooth muscle cells. Detailed examination of coexistence of these two interstitial phenomena should further clarify the cellular mechanisms involved in renal interstitial fibrosis.
Oligomerization properties of ERp29, an endoplasmic reticulum stress protein
(1998-07-24) Mkrtchiana, Souren; Baryshev, Mikhail; Matvijenko, Olga; Sharipo, Anatoly; Sandalova, Tatyana; Schneider, Gunter; Ingelman-Sundberg, Magnus; Institute of Microbiology and Virology
ERp29, a novel and ubiquitously expressed endoplasmic reticulum (ER) stress-inducible protein, was recently isolated and cDNA cloned in our laboratory. Using size exclusion chromatography and chemical cross-linking we have assessed the oligomerization properties of ERp29. Purified ERp29 in solution as well as in rat hepatoma cells self-associates predominantly into homodimers. Labeling of the cells with [35S]methionine with subsequent cross-linking and immunprecipitation showed that ERp29 interacts with a number of ER proteins, one of which was previously identified as BiP/GRP78. Secondary structure prediction and fold recognition methods indicate that the native conformation of ERp29 resembles the thioredoxin fold, a structural motif characteristic of a number of enzymes with the redox function, including protein disulfide isomerase (with which ERp29 shares limited sequence similarity). Dimerization of the protein is suggested to be advantageous for the protein binding potential of ERp29.
CTX-M-5, a novel cefotaxime-hydrolyzing β-lactamase from an outbreak of Salmonella typhimurium in Latvia
(1998-08) Bradford, Patricia A.; Yang, Youjun; Sahm, Daniel; Grope, Ilze; Gardovska, Dace; Storch, Gregory; Department of Paediatrics
At a children's hospital in Riga, Latvia, isolates identified as Salmonella typhimurium were found to be resistant to expanded-spectrum cephalosporins. Two of the resistant strains were analyzed for the mechanism of cephalosporin resistance. Isoelectric focusing revealed a common β- lactamase with a pI of 8.8. In addition, one of the strains produced a pI 7.6 β-lactamase. A transconjugant producing only the pI 7.6 enzyme was susceptible to expanded-spectrum cephalosporins; therefore, this enzyme was most likely SHV-1. Transformants producing only the pI 8.8 β-lactamase were resistant to cefotaxime and aztreonam but were susceptible or intermediate to ceftazidime. A substrate profile determined spectrophotometrically with purified enzyme revealed potent activity against cefotaxime, with a relative k(cat) value of 95 (benzylpenicillin equal to 100). The enzyme showed lower relative k(cat) values for ceftazidime (3.3) and aztreonam (9.3). In addition, the enzyme was inhibited by clavulanate, sulbactam and tazobactam, with 50% inhibitory concentrations of 19, 100, and 3.4 nM, respectively. These results indicated the presence of an unusual extended-spectrum β- lactamase. The gene expressing the pI 8.8 β-lactamase was cloned. Nucleotide sequencing revealed a β-lactamase gene that differs from the gene encoding CTX-M-2, which also originated from S. typhimurium, by 11 nucleotides, 4 of which result in amino acid substitutions: Ala27Thr, Val230Gly, Glu254Ala, and Ile278Val. These results indicated the presence of a novel extended-spectrum β-lactamase, designated CTX-M-5, that specifically confers resistance to cefotaxime.
Topical tacrolimus is not effective in chronic plaque psoriasis : A pilot study
(1998-09) Zonnevdd, Ingrid M.; Rubins, Andris; Jablonska, Stephanie; Dobozy, Attila; Ruzicka, Theo; Kind, Peter; Dubertret, Louis; Bos, Jan D.
Background: Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systemically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis. Observations: After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group. Conclusions: There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.
Identification of an N-hydroxyguanidine reducing activity of xanthine oxidase
(1998-10-01) Dambrova, Maija; Uhlén, Staffan; Welch, Christopher J.; Wikberg, Jarl E.S.
A guanoxabenz [1-(2,6-dichlorobenzylideneamino)-3-hydroxyguanidine; an N-hydroxyguanidine] reducing enzymatic activity of rat spleen cytosol was investigated by means of protein purification and N-terminal amino acid sequencing, the reducing activity was shown to reside in xanthine oxidase. The action of the enzyme on guanoxabenz resulted in the formation of guanabenz [1-(2,6-dichlorobenzylideneamino) -3-guanidine]; the product formation could be monitored by HPLC and its identity was confirmed by NMR analysis. The reduction of guanoxabenz required xanthine or NADH as reducing substrates, while the process could be blocked by allopurinol, a selective inhibitor of xanthine oxidase. By using bovine milk xanthine oxidase, the guanoxabenz reducing activity of the enzyme was also verified. We conclude that guanoxabenz is a novel electron acceptor structure for xanthine oxidase.
Cardioprotective effects of N-hydroxyguanidine PR5 in myocardial ischaemia and reperfusion in rats
(1999) Veveris, Maris; Dambrova, Maija; Cirule, Helena; Meirena, Dainuvite; Kalvinsh, Ivars; Wikberg, Jarl E.S.
1. The potential for the N-hydroxyguanidine compound PR5 (N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N'-hydroxyguanidine) as a cardioprotective agent in heart ischaemia and reperfusion injury was investigated using rat models. 2. Administration of 1-10 mg kg-1 of PR5 5 min before 10 min of left coronary artery occlusion, followed by 20 min reperfusion, strongly inhibited repel fusion burst of arrhythmias and markedly improved the survival of the animals (e.g. ventricular fibrillation incidence 93 vs 43% (P < 0.05); mortality 47 vs 0% (P < 0.05), for controls and for 3 mg kg-1 of PR5, respectively). 3. Administration of 3 mg kg-1 of PR5 1 min before reperfusion to rats subjected to 10 min occlusion, 20 min reperfusion was most effective in reducing arrhythmias and decreasing mortality (43 vs 0% P < 0.05), but effects were also seen when PR5 was administered 0, 1 and 5 min after start of reperfusion. 4. Coronary occlusion/reperfusion (10-20 min) increased malondialdehyde (MDA) of rat hearts (0.88 ± 0.13 for sham vs 1.45 ± 0.12 nmol mg-1 protein for ischaemic; P < 0.05). In rats where 3 mg kg-1 PR5 were administered 1 min before reperfusion the increase was attenuated (MDA being 1.04 ± 0.12; P < 0.05 vs ischaemic). 5. PR5 caused a substantial reduction of the infarction size in rats subjected to 180 min left coronary artery occlusion, followed by 120 min of reperfusion; the necrotic zone being 326 ± 32 mg for controls vs 137 ± 21 mg for animals treated with 3 x 3 mg kg-1 of PR5 (P < 0.01). 6. PR5 reduced the elevation of the ST-segment of the ECGs, as well as caused pronounced attenuation of the rapid blood pressure drop seen at the start of reperfusion following coronary artery occlusion. 7. We conclude that the N-hydroxyguanidine PR5 provides remarkable protection against ischaemia and reperfusion induced myocardial necrosis and life-threatening arrhythmias. These effects of PR5 are discussed in relation to a recently discovered ability of N-hydroxyguanidines to function as electron accepters at the xanthine oxidase enzyme.
Toxicity of mercury to hybridoma TA7 cells
(1999) Remez, Inessa; Andersons, Pauls; Veksler, Hackel
Environmental mercury and mercury compound contamination has increased dramatically since the industrial revolution. This paper describes the toxic effects of mercury on a culture of hybridoma TA7 cells, which produce antibodies against the A-subunit of viskumin. Cells were cultivated on 96- well flat-bottomed plates with RPMI-1640 medium supplemented with 10% fetal calf serum at 37°C in 5% CO2/95% air. The cells were exposed to 0.1nM/l- 10μM/l Hg2(NO3)2·2H2O (mercury nitrate) during the exponential growth phase. Toxicity was assessed by using the colorimetric MTT (tetrazolium) assay after exposure for 48 hours. Cell growth and cell survival were evaluated by using percentage indices of cellular content in exposed cells when compared to non-exposed control cells. The concentrations of the no- effect level, the lowest observed effect level and the the highest toxic effect level were registered. The toxic effects of the mercury compound on the hybridoma cells occurred between 0.1μM/l and 10μM/l.
Re-evaluation of phytohormone-independent division of tobacco protoplast-derived cells
(1999-03) Schell, Jeff; Bisseling, Ton; Dülz, Marion; Franssen, Henk; Fritze, Klaus; John, Michael; Kleinow, Tatjana; Leßnick, Angela; Miklashevichs, Edvins; Pawlowski, Katharina; Röhrig, Horst; Van De Sande, Karin; Schmidt, Jürgen; Steinbiß, Hans Henning; Stoll, Marion; Institute of Microbiology and Virology
We have used a [3H] thymidine incorporation assay and microscopic observation in order to reassess recently published data dealing with the response of tobacco protoplasts to phytohormones, lipochitooligosaccharides and peptides (Harling et al., 1997; Hayashi et al., 1992; Miklashevichs et al., 1996; Miklashevichs et al., 1997; Rohrig et al., 1995; Rohrig et al., 1996; van de Sande et al., 1996; Walden et al., 1994). These proliferation assays reveal that, in contrast to published data, isolated cells of the investigated mutant plant lines axi159 (Hayashi et al., 1992; Walden et al., 1994), axi4/1 (Harling et al., 1997) and cyil (Miklashevichs et al., 1997), which were generated by activation T-DNA tagging, were unable to grow in the absence of auxin or cytokinin. Furthermore, lipochitooligosaccharides which play a key role in the induction of nodules on roots of legumes were unable to promote auxin- or cytokinin-independent cell division in tobacco protoplasts as claimed by Rohrig et al. (1995, 1996). The finding of van de Sande et al. (1996) that ENOD40 confers tolerance of high auxin concentration to wild-type tobacco protoplasts was also reinvestigated. The results of our investigations show that we were unable to reproduce the proliferation data presented in this study, which were obtained by counting tobacco protoplast-derived cells undergoing division. In total, none of the published data on phytohormone-independent division of tobacco cells could be reproduced.
Diphtheritic polyneuropathy : A clinical study and comparison with Guillain-Barré syndrome
(1999-10) Logina, Inara; Donaghy, Michael; Department of Neurology and Neurosurgery
Objectives and Methods - Clinical features of 50 adults with diphtheritic polyneuropathy (DP) were studied in Riga, Latvia and compared with 21 patients with Guillain-Barré syndrome (GBS). Results - Neurological complications occurred in 15% of patients admitted to hospital with diphtheria and usually after severe pharyngeal infection. Bulbar dysfunction occurred in 98% of patients with DP and only 10% of patients with GBS. Limb weakness was mild or absent in 30% of patients with DP. Ventilation dependent respiratory failure occurred in 20% of patients with DP. The first symptoms of DP occurred 2-50 days after the onset of local diphtheria infection. Neurological deterioration in DP continued for a median of 49 (range 15-83) days and improvement started 73 (range 20-115) days after onset. In 66% of patients with DP, the neuropathy was biphasic with a secondary worsening after 40 days. By contrast patients with GBS worsened for only 10 days on average (range 2-28 days) and improved after 21 (range 4-49) days. Eight patients with DP died, four from severe cardiomyopathy and four from multiple diphtheritic organ failure. Prolonged distal motor latencies (DMLs) were common to both DP and GBS, and more pronounced than motor conduction slowing. Limb symptoms continued after 1 year in 80% of the patients with DP, 6% were unable to walk independently, but independent respiratory and bulbar function had returned in all survivors. By comparison no patients with GBS died and none were severely disabled after 1 year. No death, in patients with DP occurred after antitoxin on days 1 or 2 after onset of diphtheria symptoms, whereas identical rates of death and peak severity of DP were seen both in those who received antitoxin on days 3-6 and those who did not receive it at all. Conclusion - Diphtheric polyneuropathy is much more likely than GBS to have a bulbar onset, to lead to respiratory failure, to evolve more slowly, to take a biphasic course, and to cause death or long term disability. Antitoxin seems ineffective if administered after the second day of diphtheritic symptoms.
Neopterin and kynurenine concentrations in aqueous humour of the anterior chamber of the eye and in serum of cataract patients with pseudoexfoliation
(2000) Laganovska, G.; Martinsons, A.; Pitrans, B.; Widner, B.; Fuchs, D.; Rīga Stradiņš University
In 40 cataract patients and in 51 patients without pseudoexfoliation (PES) we determined serum concentrations of neopterin, kynurenine, and selenium and concentrations of neopterin in aqueous humour from the anterior chamber of the eye. In addition, selenium content in lenses was determined. Significantly increased kynurenine and neopterin concentrations in serum and neopterin concentrations in aqueous humour were observed in mature cataract patients with PES compared to those without. These patients also presented with the lowest content of selenium in serum and lens, compared with cataract patients without PES. Increased concentrations of neopterin in serum and aqueous humour of the anterior chamber of eyes suggest an increased degree of oxidative stress in patients with PES. Thus, the results support the role of oxidative stress in the development of PES in cataract patients. The decreased content of selenium may elicit immune system activation via an increased oxidative stress as it is indicated by the increased formation of kynurenine and neopterin.
Syphilis and gonorrhoea in the Baltic countries
(2000) Rubins, Andris Y.; Rubins, Silvestrs; Jakabsone, I.; Department of Doctoral Studies
Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis
(2000-06) Sanjeevi, C. B.; Miller, E. N.; Dabadghao, P.; Rumba, I.; Shtauvere, A.; Denisova, A.; Clayton, D.; Blackwell, J. M.
Objective. To examine the role of NRAMP1 in susceptibility to juvenile rheumatoid arthritis (JRA). Methods. DNA from 119 JRA patients (72 pauciarticular, 47 polyarticular) and 111 healthy controls from Latvia was genotyped for a functional repeat polymorphism in the promoter of NRAMP1 and a linked (<150 kb) microsatellite D2S1471. The findings were compared with those from HLA-DQ alleles typed previously. Chi-square analyses were performed using the Mantel-Haenszel test and stratification according to pure Latvian or pure Russian descent. Haplotype analysis was performed using the Associate program to implement the expectation-maximization algorithm based on the gene-counting technique. Results. Allele 3 at NRAMP1 conferred increased risk (odds ratios [ORs] 2.26, 2.31, and 2.19; P = 0.0006, 0.003, and 0.019) of disease in the JRA, pauciarticular, and polyarticular patient groups, respectively. Allele 2 conferred protection (OR 0.44, 0.43, and 0.46). Alleles at D2S1471 that conferred susceptibility (6 and 12) or protection (11) did so only when on a haplotype with alleles 3 or 2, respectively, at NRAMP1. Allele 3 at NRAMP1 was additive with HLA-DQ7 for susceptibility (OR 3.71, 3.71, and 4.02), and allele 2 at NRAMP1 was additive with HLA-DQ5 for protection (OR 0.19, 0.08, and 0.12). Conclusion. The NRAMP1 allele conferring susceptibility to JRA drives high levels of NRAMP1 expression, while the allele associated with protection drives low levels. These 2 alleles are inversely associated with susceptibility to infectious disease, consistent with their maintenance in populations through balancing selection.
Combined intraarterial/intravenous thrombolysis for acute ischemic stroke
(2001) Keris, Valdis; Rudnicka, Svetlana; Vorona, Vladimirs; Enina, Gertrude; Tilgale, Biruta; Fricbergs, Juris
BACKGROUND AND PURPOSE: The intravenous use of recombinant tissue-type plasminogen activator (rTPA) in acute ischemic stroke has been investigated in three large trials. Limited series have reflected outcome after local intraarterial thrombolysis (LIT) in the cerebral territory. The purpose of this study was to evaluate the safety and efficacy of combined intraarterial/intravenous thrombolysis using rTPA (actilyse) for acute ischemic stroke. METHODS: Forty-five patients with acute onset of severe hemispheric stroke and without signs of major cerebral infarction on early CT scans were randomized by order of admission. Twelve patients were treated with 50 mg actilyse (maximal dose, 0.7 mg/kg); three had occlusion of the internal carotid artery and nine had occlusion of the middle cerebral artery. Thrombolysis was started by LIT and continued intravenously within 6 hours of stroke onset. Outcome, assessed after 1 and 12 months according to the modified Rankin scale (MRS), was considered good (MRS score, 0-3) for patients who were functionally independent and poor (MRS score, 4-5) for those who were dependent or had died. RESULTS: In the thrombolysis group, outcome was good in eight patients at 1 month and in 10 patients at 12 months; in the control group, outcome was good in seven (21%) and 11 (33%) patients, respectively. Of the eight patients with a good outcome after thrombolysis, four had complete and one had partial recanalization. In the control group, the rate of intracerebral hemorrhage was 6%. Mortality at 1 month in the thrombolysis and control groups was 17% and 48%, respectively. CONCLUSIONS: Combined intraarterial/intravenous thrombolysis with low-dose rTPA may be a safe and effective treatment for acute ischemic stroke within 6 hours in carefully selected patients.
Thioredoxin fold as homodimerization module in the putative chaperone ERp29 : NMR structures of the domains and experimental model of the 51 kDa dimer
(2001) Liepinsh, E.; Baryshev, M.; Sharipo, A.; Ingelman-Sundberg, M.; Otting, G.; Mkrtchian, S.
Background: ERp29 is a ubiquitously expressed rat endoplasmic reticulum (ER) protein conserved in mammalian species. Fold predictions suggest the presence of a thioredoxin-like domain homologous to the a domain of human protein disulfide isomerase (PDI) and a helical domain similar to the C-terminal domain of P5-like PDIs. As ERp29 lacks the double-cysteine motif essential for PDI redox activity, it is suggested to play a role in protein maturation and/or secretion related to the chaperone function of PDI. ERp29 self-associates into 51 kDa dimers and also higher oligomers. Results: 3D structures of the N- and C-terminal domains determined by NMR spectroscopy confirmed the thioredoxin fold for the N-terminal domain and yielded a novel all-helical fold for the C-terminal domain. Studies of the full-length protein revealed a short, flexible linker between the two domains, homodimerization by the N-terminal domain, and the presence of interaction sites for the formation of higher molecular weight oligomers. A gadolinium-based relaxation agent is shown to present a sensitive tool for the identification of macromolecular interfaces by NMR. Conclusions: ERp29 is the first eukaryotic PDI-related protein for which the structures of all domains have been determined. Furthermore, an experimental model of the full-length protein and its association states was established. It is the first example of a protein where the thioredoxin fold was found to act as a specific homodimerization module, without covalent linkages or supporting interactions by further domains. A homodimerization module similar as in ERp29 may also be present in homodimeric human PDI.

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