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F Wunderlich

Publications and source records attributed to F Wunderlich.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cadmium-detoxification in the earthworm Enchytraeus: specific expression of a putative aldehyde dehydrogenase.

The ubiquitous earthworm Enchytraeus buchholzi is provided with a very effective, but still unknown, mechanism of Cadmium (Cd)-detoxification, a central role in which has been ascribed to the Cd-inducible crp-gene encoding a novel cysteine-rich, non-metallothionein 25 kDa protein. This study identifies another Cd-responsive gene by differential screening of a cDNA-library constructed from Cd-exposed E. buchholzi. The isolated cDNA-clone designated Ebaldh encodes a putative aldehyde dehydrogenase. Northern blot analysis shows that the Ebaldh-expression is strongly enhanced by Cd, but remains unaffected by other stressors such as Zn, Hg, and H2O2. This Cd-specificity of Ebaldh suggests that Cd-detoxification in E. buchholzi requires low intracellular concentrations of aldehydes which are known to target sulfhydryl groups thus inactivating the Cd-binding capacity of CRP.

Aldehyde Dehydrogenase↗
PubMed1996

Earthworm gene as indicator of bioefficacious cadmium.

The expression of a novel Cd-inducible gene encoding a 25 kDa non-metallothionein cysteine-rich protein (CRP) in the earthworm Enchytraeus buchholzi is investigated with respect to Cd-specificity and Cd-sensitivity. The amount of CRP-mRNA correlates with the environmental as well as with the intra-worm Cd-concentration. Even the subtoxic concentration of 100 microgram Cd/1 induces CRP-gene expression. CRP-mRNA is expressed already 2 h after the worms were exposed to Cd. Other heavy metals or stress conditions can induce only little or even no CRP-mRNA. The CRP-gene is switched on long before Cd becomes toxic to worms and can be therefore taken as a warning signal of prospective irreversible Cd-damages at an early, still reversible stage.

Amino Acid Sequence↗
PubMed1995

Egg deposition of the intestinal nematode Heterakis spumosa: stimulation by soluble colon factors of mice.

The nematode Heterakis spumosa lives and develops in the upper colon of mice. The colon mucosa contains soluble factors that significantly increase release of eggs by female H. spumosa in vitro. Egg release is stimulated more when colon factors are prepared from mice harboring adult H. spumosa. Also, soluble factors stimulating egg release can be prepared from homogenates of H. spumosa but are not contained in H. spumosa-conditioned medium. Moreover, soluble factors from the small intestine of mice infected with Heligmosomoides polygyrus also stimulate egg release by H. spumosa females in vitro to about the same extent as soluble factors from the colon of H. spumosa-infected mice. Our data suggest that colon factors are involved in the regulation of egg deposition of H. spumosa, the efficiency of these factors is increased by intestinal inflammation, and that these factors are accumulated by H. spumosa worms.

Animals↗
PubMed1994

cDNA cloning of a cadmium-inducible mRNA encoding a novel cysteine-rich, non-metallothionein 25-kDa protein in an enchytraeid earthworm.

Cadmium accumulation and its effect on gene expression have been investigated at sublethal cadmium concentrations in the soil oligochaete Enchytraeus buchholzi. This worm is capable of accumulating cadmium to large amounts, which coincides with the induction of a mRNA isolated as a cDNA clone by differential screening of a cDNA library constructed from cadmium-treated enchytraeids. The cDNA clone designated CRP1 is 1474 base pairs in length and contains a 753-base pair open reading frame, encoding a novel Cys-rich non-metallothionein protein. In vitro translation of the in vitro transcribed CRP1 results in a protein with a molecular mass of 25 kDa and an pI of approximately 7.5. These values are consistent with those predicted from the deduced amino acid sequence. The CRP protein contains 27% Cys, most of them arranged in Cys-X-Cys and Cys-Cys segments. The sequence is also characterized by a 31-amino-acid motif, which is tandemly repeated along the sequence. Northern blot analysis reveals that the CRP gene is not constitutively expressed in untreated worms, but rather it is rapidly induced by cadmium. The CRP gene may be a promising candidate gene for monitoring bioavailable cadmium at subtoxic levels in terrestric environments.

Amino Acid Sequence↗
PubMed1994

Cadmium-induced mRNA encoding a nonmetallothionein 33-kDa protein in Enchytraeus buchholzi (Oligochaeta).

Enchytraeus buchholzi (Oligochaeta) were exposed to various concentrations of CdCl2 in agar and aqueous solution. The Cd uptake was determined by atomic absorption spectroscopy as well as Cd effects on survival, reproduction, and mRNA synthesis by in vitro translation of total RNA in a rabbit reticulocyte lysate system. Although Cd was rapidly accumulated by the worms, any acute toxic Cd effects at concentrations below 4 mg Cd/liter were not detectable. However, such subtoxic Cd concentrations caused the induction of an mRNA species coding for a nonmetallothionein 33-kDa protein as revealed by 2D electrophoresis of in vitro translated in vitro translated proteins using [35S]methionine. The Cd-induced synthesis of this transcriptionally regulated protein might be a preindicator for a Cd intoxication in enchytraeids.

Animals↗
PubMed1993

Testosterone impairs efficacy of protective vaccination against P. chabaudi malaria.

Vaccination with surface membranes isolated from Plasmodium chabaudi-infected erythrocytes can protect B10.A mice from the lethal outcome of P. chabaudi malaria. However, the efficacy depends on gender and testosterone levels. Thus, vaccination protects over 90% of female mice, but only about 55% of male mice and only about 34% of female mice when pretreated with testosterone for 4 weeks. The suppressive testosterone effect remains imprinted in females even at 10 weeks after the testosterone treatment. These data indicate that not only genetic but also environmental factors restrict the host's immune response to a malaria vaccine.

Animals↗
PubMed1993

Testosterone-induced changes in phosphatidylcholine molecular species composition of Plasmodium chabaudi-infected erythrocytes.

This study is concerned with the influence of testosterone on the phospholipid class and the phosphatidylcholine molecular species composition of various fractions obtained from the blood of Plasmodium chabaudi-infected mice. Blood plasma, infected erythrocytes, isolated parasites and erythrocyte membranes isolated from both non-infected and infected erythrocytes in the form of ghosts were analysed. In general, the phospholipid classes remained unaffected, while the phosphatidylcholine (PC) molecular species composition showed differences after testosterone treatment. In infected erythrocytes, there was a decrease in 16:0/20:4-PC and 18:0/20:4-PC and an increase in 16:0/18:2(16:0/20:3)-PC. The decrease of 16:0/20:4-PC was exclusively confined to parasites. The rise in 16:0/18:2(16:0/20:3)-PC and the diminution of 18:0/20:4-PC occurred in the erythrocyte membrane of both infected ghosts and non-infected ghosts as well as in the blood plasma. It is suggested that these changes occur primarily in the plasma thereby influencing the erythrocyte membranes. The decrease in 16:0/20:4-PC supports the view of the independence of the parasite from the biosynthetic lipid pathways of its host cell.

Animals↗
PubMed1993

Testosterone-induced compared with oestradiol-induced immunosuppression against Plasmodium chabaudi malaria.

Testosterone suppresses immunity against malaria caused by Plasmodium chabaudi in B10 mice. Since this effect is probably not mediated through the classical androgen-receptor response, we investigated whether testosterone might act, after aromatization to oestradiol (OE2), through the oestrogen receptor (ER). Indeed, OE2 was found to act immunosuppressively when used at only about 1% of the immunosuppressive dose of testosterone. This becomes evident as an OE2-induced suppression of self-healing of P. chabaudi infections in female and castrated male B10 mice. The immunosuppressive OE2 effect is associated with a 16-fold increase in the circulating level of OE2 and can be prevented by ER blockers such as tamoxifen and clomifene. In contrast, the immunosuppressive effect of testosterone, which is not associated with any changes in the level of OE2, cannot be abolished by ER blockers or by aromatase inhibitors, such as atamestane and drofazar hydrochloride. Moreover, OE2 and testosterone act differently on spleen cells; OE2 induces a decrease in CD(4+)-T-cells, whereas testosterone causes an increase in CD(8+)-T-cells and a decrease in total nucleated spleen cells. The immunosuppressive effect of testosterone, but not that of OE2, can be adoptively transferred to syngeneic mice by nucleated spleen cells, predominantly T-cells. Our data show that the immunosuppressive activity of testosterone, in contrast to OE2, is not mediated through the ER. The immunosuppressive action of testosterone is therefore thought to be primarily mediated through a non-genomic mechanism.

Animals↗
PubMed1992

Plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity.

This study investigates the effect of estradiol (E) on self-healing of Plasmodium chabaudi malaria in mice of the inbred strain C57BL/10. Our data show: (1) Female mice and male castrates are capable of self-healing infections when challenged with 10(6) P. chabaudi-infected erythrocytes. Self-healing is completely suppressed after pretreatment of mice with 12 micrograms E injected sc twice a week for 3 weeks. (2) The suppressive effect of E is prevented by the estrogen receptor blockers tamoxifen and clomiphene. (3) The nonsteroidal E-agonist diethylstilbestrol (DES) also suppresses self-healing. This suppressive DES effect is prevented by tamoxifen. (4) In mice immune to P. chabaudi, neither survival rate nor the course of parasitemia is affected by E, even at 10-fold higher E doses. Our data suggest that the immunosuppressive action of E is a specific genomic effect, i.e., E-induced gene products prevent the development of protective immunity against P. chabaudi.

Animals↗
PubMed1992

Testosterone-induced diminution of two peptides in spleen cells from testosterone-immunosuppressed B10 mice.

High-performance liquid chromatography (HPLC) is used to detect testosterone (T)-sensitive peptides in spleen cells isolated from female C57BL/10 mice immunosuppressed against Plasmodium chabaudi malaria by T treatment. Two peaks with retention times of about 25 min and 34 min, respectively, were identified to be diminished by about 52% and 47%, respectively, in spleen cells from T-treated mice compared to those from untreated mice. Amino acid sequencing revealed that the 24 min peak consisted of the dipeptide Met-Phe and the 34 min peak contained a degradative fragment of the alpha-chain of hemoglobin. Our data suggest that the immunosuppressive T treatment of B10 mice induces a perturbation of erythrophagocytosis in spleens.

Amino Acid Sequence↗
PubMed1992

Effects of testosterone on Heterakis spumosa infections in mice.

This study describes the effects of testosterone (Te) on the intestinal nematode Heterakis spumosa in mice. The course of Heterakis infections is apparently under Te-control. At high circulating Te-levels as occurring in intact males, Te-treated females, and Te-treated castrated males, the period of release of Heterakis eggs in mouse faeces is greatly extended and the number of eggs released per unit time is markedly elevated in comparison to low Te-levels, as found in untreated females and castrated male mice. Also, the onset of the patent period occurs earlier in Te-treated mice. Testosterone also accelerates development and growth of both female and male worms of Heterakis in mice. Thus, young adult male worms can be observed in the upper colon of Te-treated castrated male mice on day 21 post-infection (p.i.), whereas, at that time, only L4 larvae are present in Te-untreated male castrates. Testosterone also favours the survival of nematodes in hosts. In untreated male castrates, the number of worms present on day 7 p.i. (L2 larvae) is approximately two thirds higher than that found on day 21 p.i. However, such a reduction in the number of worms does not occur in Te-treated castrated mice during the same period of time. The early phases of the life-cycle of Heterakis, i.e. hatching in the small intestine and final settling of L2 larvae in the upper colon are independent of Te. Also, Te does not affect motility and even slightly reduces the fecundity of adult female worms in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Testosterone-unresponsiveness of existing immunity against Plasmodium chabaudi malaria.

Testosterone (Te) is known to suppress immunity and to increase host susceptibility to many parasites. This study investigates the action of Te on immunity acquired against blood-stages of the malaria parasite Plasmodium chabaudi in female mice of the inbred strain C57BL/10. Our data show: (i) About 90% of mice infected with 10(6) P. chabaudi-infected erythrocytes are able to develop protective immune mechanisms which become evident in self-healing the infection. The capability of self-healing is lost when mice are pretreated with Te for 3 weeks. (ii) Mice which have self-healed infections acquire immunity to homologous rechallenge. Concomitantly, mice become Te-unresponsive in that their acquired immunity is not suppressible by Te-treatment. (iii) Flow cytometry reveals that Te-pretreatment entails an increase of CD8+ cells and a decrease of Ig+ cells by about 4% in spleens of non-immune mice. In immune mice, however, there is a Te-unresponsiveness of the percental distribution of splenic cell populations. (iv) Adoptive transfer experiments indicate that immunity is conferred by spleen cells, presumably non-T-cells. These cells are Te-unresponsive, since they exert their effect in Te-pretreated mice in the presence of Te. (v) Te-unresponsive immunity can be also transferred by serum, especially the IgG-fraction, obtained from immune mice. Our data demonstrate that Te prevents the development of protective immunity against P. chabaudi infections. However, when once established, protective immunity becomes unresponsive to Te. Our data suggest that the effector mechanisms of protective immunity involve Te-unresponsive B cells secreting protective IgG-antibodies.

Animals↗
PubMed1992

Testosterone-induced suppression of self-healing Plasmodium chabaudi malaria: an effect not mediated by androgen receptors?

This study investigates whether androgen receptors (AR) mediate the suppressive effect of testosterone on self-healing Plasmodium chabaudi malaria. Our data show the following. (1) Female and castrated male mice of the inbred strain C57BL/10 self-heal and survive infections when challenged with 10(6) P. chabaudi-parasitized erythrocytes. However, self-healing is prevented when circulating testosterone levels are high as in intact males or in females and castrated males pretreated with 0.9 mg testosterone twice a week for 3 weeks. (2) The lethal outcome of P. chabaudi in intact males is not affected by different doses of AR blockers such as cyproterone acetate, cyproterone, flutamide and nilutamide when applied at least 3 weeks before infection and during infection. Also, these AR blockers do not impair the testosterone-induced lethal outcome of infections in testosterone-treated females and castrated males. (3) Tfm mice possessing mutant non-functional ARs and normal 'male' testosterone levels succumb to infection with P. chabaudi. However, the corresponding wild-type mice possessing functioning ARs are able to resist P. chabaudi infections at low circulating testosterone levels. (4) In contrast to testosterone, testosterone metabolites such as 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone, androsterone and 1-dehydrotestosterone cannot suppress self-healing in castrated male B10 mice. Our data suggest that testosterone suppresses the development of protective immunity against P. chabaudi malaria, and that this immunosuppressive effect of testosterone is not primarily mediated by the classical AR response.

Animals↗
PubMed1991

Distinct lipid compositions of parasite and host cell plasma membranes from Plasmodium chabaudi-infected erythrocytes.

Mouse erythrocytes infected with early or late trophozoites of the malaria parasite Plasmodium chabaudi were fractionated into free parasites and host cell plasma membranes, and both fractions were analyzed for cholesterol content and the composition of phospholipids and total fatty acids. The major results are: (i) parasites contain only a very low level of cholesterol which is about one-tenth of that of host cell plasma membranes. (ii) Parasites also contain less sphingomyelin and phosphatidylserine as well as more phosphatidylcholine than host cell plasma membranes. (iii) Parasites contain less 18:0 and 18:1 and more 18:2 and 20:4 fatty acids than host cell plasma membranes. (iv) During intraerythrocytic growth of parasites from early to late trophozoites, the relative proportions of cholesterol and phospholipids remain largely unchanged in both parasites and host cell plasma membranes. However, significant changes occur in the fatty composition of both compartments. There is an increase in the 20:4 and a decrease in the 18:0 and 18:1 fatty acids. (v) Plasma membranes of infected and non-infected erythrocytes exhibit about the same cholesterol content and phospholipid composition, but differ in the total fatty acid composition. Our data suggest the existence of distinct mechanisms controlling the different lipid compositions of parasites and host cell plasma membranes in whole Plasmodium chabaudi-infected erythrocytes during intraerythrocytic development of parasites, though both compartments are known to depend on the supply of various lipids from the host.

Animals↗
PubMed1991

Testosterone-induced susceptibility to Plasmodium chabaudi malaria: variant protein expression in functionally changed splenic non-T cells.

This study investigates the effects of the male sex hormone, testosterone (Te), on self-healing of Plasmodium chabaudi malaria as well as on protein expression and functional properties of total spleen cells and splenic T cells in females of the mouse strain C57BL/10. About 90% of the B10 females survive a challenge with 10(6) P. chabaudi-infected erythrocytes. The percentage of self-healers, however, is reduced to about 60%, 40%, and 0% after pretreatment with Te for 1, 2, and 3 weeks, respectively. The progressive loss of the capability of self-healing is correlated with an increasing expression of five proteins in splenic non-T cells as revealed by two-dimensional fluorography after metabolic labelling of total spleen cells and T cells with [35S]methionine. These have molecular masses (isoelectric points) of about 10 kDa (pI 5.7), 14 kDa (pI 6.3), 14 kDa (pI 6.4), 38 kDa (pI 6.5), and 46 kDa (pI 5.5), respectively. Splenic non-T cells from mice treated with Te for 3 weeks have gained an increased capability to stimulate the concanavalin A-induced proliferative response of T cells. Te induces the changes in functional properties and protein expression of splenic non-T cells only in vivo and not in vitro. This suggests that the changes in splenic non-T cells as well as the prevention of self-healing P. chabaudi malaria are not directly induced by Te but rather indirectly, i.e. by a Te metabolite and/or Te-induced factor(s).

Animals↗