Biomedical subjects

P E Olsson

Publications and source records attributed to P E Olsson.

At least 19 recordsLinked to original sources

PubMed2005

Novel steroidogenic factor-1 homolog (ff1d) is coexpressed with anti-Mullerian hormone (AMH) in zebrafish.

ff1d is a novel zebrafish FTZ-F1 gene with sequence characteristics indicating similar basic regulatory mechanisms as the previously characterized ff1 based on the presence of an FTZ-F1 box in the DNA binding domain and an interactive domain (I-Box) and an AF-2 in the ligand binding domain. The highest sequence similarity was found between ff1d and ff1b (NR5A4), a gene previously shown to be a functional homolog to the steroidogenic factor 1 (SF-1). The expression pattern of ff1d was comparable to ff1b both in brain and gonads in adults and in the pituitary and interrenal cells in embryos. SF-1 is crucial in mammalian steroidogenesis and in sex determination by regulating the anti-Mullerian hormone (AMH). In fish, AMH has not been described previously. In this study, we cloned a partial zebrafish AMH. AMH was detected in growing oocytes, the ovarian follicular layer and testicular Sertoli cells, similar to the mammalian pattern, suggesting a conserved role between zebrafish and mammalian AMH. Teleosts lack a gene homolog to SRY, which constitute the universal testis-determining factor in mammalian sex determination. Comparison of sequences and expression patterns indicate that ff1d is a new candidate for sex determination and differentiation in a way similar to SF-1, possibly involving AMH.

Amino Acid Sequence↗

PubMed2004

Regulation of Arctic char (Salvelinus alpinus) egg shell proteins and vitellogenin during reproduction and in response to 17beta-estradiol and cortisol.

Estrogens induce both vitellogenin (Vtg) and egg shell (zona pellucida; ZP) protein synthesis in salmonids. However, while Vtg is strictly under estrogenic control, recent reports suggest that additional mechanisms are involved in ZP protein synthesis. During sexual maturation both estrogen and glucocorticoid levels increase in the circulation of female fish. As glucocorticoids have been shown to interfere with Vtg induction in fish we investigated whether cortisol (F) had similar effects on ZP regulation. In the present study we determined both the natural variation in Vtg and ZP during an annual reproductive cycle in female Arctic char (Salvelinus alpinus), and the effect of co-treatment of juvenile Arctic char with 17beta-estradiol (E2) and F. During sexual maturation the expression of Vtg and ZP correlated to plasma levels of E2 and F. Determination of Vtg and ZP protein levels following co-treatment with E2 and F showed that F antagonized E2 induction of Vtg. However, F was observed to potentiate the expression of ZP protein in the same fish. These results indicate that in Arctic char Vtg and ZP proteins are not regulated by the same mechanisms and suggest that ZP protein expression does not necessarily imply exposure to estrogenic compounds alone, and may thus not be ideally suited as a biomarker of exposure to estrogenic compounds.

Animals↗

PubMed2001

Molecular cloning and characterization of spiggin. An androgen-regulated extraorganismal adhesive with structural similarities to von Willebrand Factor-related proteins.

One of the most definitive examples of a vertebrate extraorganismal structural protein can be found in three-spined sticklebacks (Gasterosteus aculeatus). In the breeding male the kidney hypertrophies and synthesizes an adhesive protein called "spiggin," which is secreted into the urinary bladder from where it is employed as a structural thread for nest building. This paper describes the first molecular characterization of spiggin and demonstrates that this adhesive is a protein complex assembled from a potential of three distinct subunits (alpha, beta, and gamma). These subunits arise by alternative splicing, and 11-ketoandrogens induce their expression in stickleback kidneys. Analysis of the predicted amino acid sequence of each subunit reveals a modular organization whose structural elements display a similarity to the multimerization domains found within von Willebrand Factor-related proteins. These results implicate that spiggin utilizes a conserved multimerization mechanism for the formation of a viscous agglutinate from its constituent subunits in the urinary bladders of male sticklebacks. This novel extraorganismal structural protein is therefore ideally suited to its function as an adhesive thread.

Adhesives↗

PubMed2001

Developmental expression patterns of FTZ-F1 homologues in zebrafish (Danio rerio).

The fushi tarazu factor 1 (FTZ-F1) gene family constitutes a subgroup of orphan nuclear receptors which can be divided into two groups (LRH/FTF- and SF-1/Ad4BP-like) based on sequence homology, function, and tissue distribution. Analysis of zebrafish FTZ-F1 homologues (zFF1 and ff1b) during embryogenesis indicated distinct expression patterns for both genes. Besides the previously observed expression in pituitary/hypothalamus and mandibular arch, zFF1 transcripts were also detected in domains corresponding to the pronephric duct, somites, liver, and hindbrain. Additionally, ff1b transcripts were detected at other developmental stages than earlier documented. Comparative sequence analysis showed that zFF1 exhibited higher sequence similarity to the LRH/FTF group than the SF-1/Ad4BP group, whereas ff1b was indistinguishable between the groups. These observations, coupled with obtained expression patterns, indicate that zebrafish FTZ-F1 homologues exhibit characteristics that are indicative of both LRH/FTF- and SF-1/Ad4BP-like genes.

Animals↗

PubMed2001

Expression of three vitelline envelope protein genes in arctic char.

Several studies have shown effects of estrogenic substances on endocrine and reproductive systems in wildlife. Measurement of plasma vitellogenin (VTG) is a commonly used method to determine exposure to estrogenic substances in fish. There is, however, a growing need for additional sensitive and accurate methods to detect estrogenic substances in vivo. The vitelline envelope proteins (VEPs) have been suggested, in other studies, as suitable biomarkers for estrogenic substances. The present study investigates the induction of VEPs in juvenile Arctic char (Salvelinus alpinus). The results demonstrate that VEP mRNA exhibits earlier induction than estrogen receptor mRNA or VTG mRNA following injection of juvenile Arctic char with a single dose of 17beta-estradiol (E2; 10 mg/kg bw). These results indicate that the VEPs have a higher sensitivity for E2 than VTG. However, an early and sex-independent expression of VEPbeta in estrogen-unchallenged juvenile Arctic char was observed. These findings suggests that the regulatory mechanisms of VEPs might be more complex than previously thought, which in turn may have implications for the usage of VEPs as biomarkers for xenoestrogen exposure.

Animals↗

PubMed2001

Bioaccumulation of selected PCBs in zebrafish, three-spined stickleback, and arctic char after three different routes of exposure.

The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

Administration, Oral↗

PubMed2001

Generating transparent zebrafish: a refined method to improve detection of gene expression during embryonic development.

In zebrafish (Danio rerio) pigmentation is initiated during embryogenesis and begins in the retinal epithelium and in the melanophores. The pigment cells develop rapidly, and within hours they constitute a prominent feature of the embryo. In order to improve signal detection by whole mount in situ hybridization, confocal microscopy, or expression of GFP, embryos may be treated with 1-phenyl 2-thiourea (PTU) during embryogenesis. PTU inhibits melanogenesis by blocking all tyrosinase-dependent steps in the melanin pathway but can be toxic at high concentrations. The embryos remain transparent as long as the PTU treatment is continued. However, PTU treatment must be initiated before the initial pigmentation because it does not remove already formed pigment. Here we provide a protocol for generating transparent zebrafish while avoiding the toxic and teratogenic effects of PTU treatment.

Journal Article↗

PubMed2001

Cloning of rainbow trout egg envelope proteins: members of a unique group of structural proteins.

All vertebrate eggs are surrounded by an extracellular envelope that protects the egg and is vital for a successful fertilization. The terminology and functions of the egg envelope vary in different vertebrate groups, but the envelope itself is consistently composed of a few major proteins that are deposited around the oocyte during oocyte growth. Here, we describe the deduced amino acid sequences and tissue expression patterns of the three major egg envelope proteins for rainbow trout (Oncorhynchus mykiss). All three vitelline envelope proteins (VEPs) are expressed in the livers of both male and female fish, with higher expression in females. In addition, VEPgamma mRNA is also detected in the female gonads. To our knowledge, this is the first time that expression of a VEP protein gene has been demonstrated to occur in more than one organ. Sequence comparison reveals that all three VEP proteins share distinct homology with their amphibian, avian, and mammalian counterparts. Whereas mammalian zona pellucida protein 3 isoforms contain two conserved serines needed for sperm binding, these are not conserved in teleost species, in which sperm entry is restricted to the micropyle. Besides the difference in VEPgamma sperm-binding function, the high sequence homology suggests that the egg envelope proteins from these distinct vertebrate groups share a common ancestry and form a unique group of structural proteins.

Amino Acid Sequence↗

PubMed2001

Analysis of the pmsCEAB gene cluster involved in biosynthesis of salicylic acid and the siderophore pseudomonine in the biocontrol strain Pseudomonas fluorescens WCS374.

Mutants of Pseudomonas fluorescens WCS374 defective in biosynthesis of the fluorescent siderophore pseudobactin still display siderophore activity, indicating the production of a second siderophore. A recombinant cosmid clone (pMB374-07) of a WCS374 gene library harboring loci necessary for the biosynthesis of salicylic acid (SA) and this second siderophore pseudomonine was isolated. The salicylate biosynthesis region of WCS374 was localized in a 5-kb EcoRI fragment of pMB374-07. The SA and pseudomonine biosynthesis region was identified by transfer of cosmid pMB374-07 to a pseudobactin-deficient strain of P. putida. Sequence analysis of the 5-kb subclone revealed the presence of four open reading frames (ORFs). Products of two ORFs (pmsC and pmsB) showed homologies with chorismate-utilizing enzymes; a third ORF (pmsE) encoded a protein with strong similarity with enzymes involved in the biosynthesis of siderophores in other bacterial species. The region also contained a putative histidine decarboxylase gene (pmsA). A putative promoter region and two predicted iron boxes were localized upstream of pmsC. We determined by reverse transcriptase-mediated PCR that the pmsCEAB genes are cotranscribed and that expression is iron regulated. In vivo expression of SA genes was achieved in P. putida and Escherichia coli cells. In E. coli, deletions affecting the first ORF (pmsC) diminished SA production, whereas deletion of pmsB abolished it completely. The pmsB gene induced low levels of SA production in E. coli when expressed under control of the lacZ promoter. Several lines of evidence indicate that SA and pseudomonine biosynthesis are related. Moreover, we isolated a Tn5 mutant (374-05) that is simultaneously impaired in SA and pseudomonine production.

Bacterial Proteins↗

PubMed2001

Effects of 17 beta-estradiol on levels and distribution of metallothionein and zinc in squirrelfish.

Females of the squirrelfish family (Holocentridae) accumulate higher levels of zinc in the liver than any other known animal. This zinc accumulation is made possible by high expression of the zinc-binding protein, metallothionein (MT). In the present study, the squirrelfish (Holocentrus ascensionis) MT cDNA was cloned and sequenced. The deduced amino acid sequence was very similar to other teleost MT. The role of estrogens on zinc metabolism was investigated by injecting male and immature female squirrelfish with 17 beta-estradiol (E(2)). E(2) treatment triggered transient increases in plasma zinc and vitellogenin (VTG) levels, and both of these variables showed very similar time courses. These results suggest that E(2) is responsible for the large hepatoovarian translocation of zinc observed in female squirrelfish and that VTG might be a vehicle for zinc. E(2) did not directly alter the levels of zinc or MT mRNA in the liver. However, the hepatic MT protein concentration increased differentially in the nuclear fraction. Thus E(2) is probably responsible for the association of MT with the nuclear fraction previously observed in untreated mature female squirrelfish.

Amino Acid Sequence↗

PubMed2000

Expression of cold-adapted beta-tubulins confer cold-tolerance to human cellular microtubules.

Isolated microtubule proteins from the cold-adapted fish, Atlantic cod (Gadus morhua), assemble at temperatures between 8 and 30 degrees C, while avian and mammalian microtubules normally do not assemble at temperatures below 20 degrees C. Tubulin, the main component in microtubules, is expressed as many isotypes. Microtubules with different isotype composition have been shown to have different dynamic properties in vitro. Our hypothesis was that cold-tolerance of microtubules is caused by tubulin isotypes that differ in the primary sequence compared to mammalian tubulins. Here we show that transfection of human HepG2 cells with cod beta-tubulin induced cold-adaptation of the endogenous microtubules. Incorporation of one single tubulin isotype can induce cold-tolerance to cold-intolerant microtubules. Three cod beta-tubulin isotypes were tested and two of these (beta1 and beta2) transferred cold-tolerance to HepG2 microtubules, thus not all cod beta-tubulins were able to confer cold-stability.

Acclimatization↗

PubMed2000

Two estrogen receptors expressed in the teleost fish, Sparus aurata: cDNA cloning, characterization and tissue distribution.

Estrogen is an essential hormone for many reproductive and non-reproductive functions. The function of estrogen in the reproductive cycle of seabream (Sparus aurata), a protandrous hermaphrodite teleost fish, is complex but it is understood to be involved in sex inversion, a process that occurs in some individuals during the second reproductive season. Estrogen action is mediated by two estrogen receptor (ER) subtypes designated alpha and beta. As a step to understanding the mechanisms of estrogen action during natural and induced sex reversal in seabream, we have isolated two cDNAs encoding distinct forms of ER homologous to mammalian ERalpha and ERbeta. The seabream ERalpha clone (sbERalpha1), which was truncated in the A/B domain, corresponded to a variant differing in five amino acids from another recently cloned sbERalpha. The ERbeta clone (sbERbeta) encoded a protein 559 amino acids long and showed only 40% identity to sbERalpha. Northern blot analysis of liver and ovary mRNA indicated the presence of several transcripts of the two receptor subtypes. PCR analysis showed that the two receptors differed in their expression pattern. sbERalpha had a more restricted distribution, occurring mainly in testis, liver and heart, and sbERbeta was present in most tissues, being more abundant in ovary, testis, liver, intestine and kidney. The presence in seabream of two ERs with several ER transcripts and their pattern of distribution are consistent with the widespread effects of estrogen in different tissues.

Amino Acid Sequence↗

PubMed1999

Identification of betaIII- and betaIV-tubulin isotypes in cold-adapted microtubules from Atlantic cod (Gadus morhua): antibody mapping and cDNA sequencing.

Isolated microtubule proteins from the Atlantic cod (Gadus morhua) assemble at temperatures between 8 and 30 degrees C. The cold-adaptation is an intrinsic property of the tubulin molecules, but the reason for it is unknown. To increase our knowledge of tubulin diversity and its role in cold-adaptation we have further characterized cod tubulins using alpha- and beta-tubulin site-directed antibodies and antibodies towards posttranslationally modified tubulin. In addition, one cod brain beta-tubulin isotype has been sequenced. In mammals there are five beta-tubulins (betaI, betaII, betaIII, betaIVa and betaIVb) expressed in brain. A cod betaIII-tubulin was identified by its electrophoretic mobility after reduction and carboxymethylation. The betaIII-like tubulin accounted for more than 30% of total brain beta-tubulins, the highest yield yet observed in any animal. This tubulin corresponds most probably with an additional band, designated beta(x), which was found between alpha- and beta-tubulins on SDS-polyacrylamide gels. It was found to be phosphorylated and neurospecific, and constituted about 30% of total cod beta-tubulin isoforms. The sequenced cod tubulin was identified as a betaIV-tubulin, and a betaIV-isotype was stained by a C-terminal specific antibody. The amount of staining indicates that this isotype, as in mammals, only accounts for a minor part of the total brain beta-tubulin. Based on the estimated amounts of betaIII- and betaIV-tubulins in cod brain, our results indicate that cod has at least one additional beta-tubulin isotype and that beta-tubulin diversity evolved early during fish evolution. The sequenced cod betaIV-tubulin had four unique amino acid substitutions when compared to beta-tubulin sequences from other animals, while one substitution was in common with Antarctic rockcod beta-tubulin. Residues 221, Thr to Ser, and 283, Ala to Ser, correspond in the bovine tubulin dimer structure to loops that most probably interact with other tubulin molecules within the microtubule, and might contribute to cold-adaptation of microtubules.

Adaptation, Physiological↗

PubMed1999

Assessment of PCBs and hydroxylated PCBs as potential xenoestrogens: In vitro studies based on MCF-7 cell proliferation and induction of vitellogenin in primary culture of rainbow trout hepatocytes.

In the present study, four structurally diverse polychlorinated biphenyls (PCBs) were chosen from a set of 20 PCBs selected to represent the 154 tetra- through hepta-chlorinated biphenyls. The purpose was to determine estrogenic activities of the chosen PCBs and five of their hydroxylated derivatives (OH-PCBs). A human breast cancer cell line (MCF-7) and primary cultures of rainbow trout (Oncorhyncus mykiss) hepatocytes were used to determine estrogenic effects. The PCBs 2,2',4,6,6'-pentachlorobiphenyl (104) and 2,2',3, 4', 5,6,6'-heptachlorobiphenyl (188), and the hydroxylated PCBs 2,2', 4',6'-tetrachloro-4-biphenylol (4'-50), 2',4', 6'-trichloro-4-biphenylol (4'-30), 2',3,5, 5'-tetrachloro-4-biphenylol (4'-72), 2',3,3',5', 6'-pentachloro-4-biphenylol (4'-112), and 2',3,4',5, 6'-pentachloro-4-biphenylol (4'-121) significantly increased MCF-7 cell proliferation. The coaddition of hydroxytamoxifen, an estrogen antagonist, inhibited increased cell proliferation. The activity of the hydroxylated PCBs 4'-50 and 4'-30 was significantly higher at all nominal concentrations tested as compared to the corresponding PCB, viz., PCB 104. The hydroxylated PCBs 4'-50, 4'-30, 4'-72 and 4'-112 induced vitellogenin synthesis in rainbow trout hepatocytes. Significant differences were found in the MCF-7 system between the parent PCB and its hydroxylated derivative, viz., for 4'-50/4'-30 and 104, and in the rainbow trout hepatocyte assay between 4'-112 and 112, respectively. No activity was observed for PCB 58 in any of the two assays in the present study. Even though cells from two different species (human and fish) are used in the present study, the results obtained by the two methods agree fairly well. In both studies the hydroxylated PCBs were more active than the PCBs, and 4'-30 was the most active compound second only to 17beta-estradiol. http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p145.html

Animals↗

PubMed1997

Functional comparison of the metal-regulated transcriptional control regions of metallothionein genes from cadmium-sensitive and tolerant fish species.

The promoter region of teleost metallothioneins (MTs) contains multiple metal-responsive elements (MREs) organized in proximal and distal clusters which together mediate gene induction by heavy metals. This arrangement of MREs is found both in cadmium-sensitive species, such as the rainbow trout, and in cadmium-tolerant species such as the pike and the stone loach. On comparison of the putative regulatory elements identified within the 5'-flanking region of these genes the major differences are that the number of MREs differ between the different species and that, while both the stone loach and rainbow trout MT genes contain TATA boxes, the pike MT gene has a TTTA box. In order to investigate if the metal sensitivity of a species is correlated to the regulatory potential of the putative MT detoxification system the promoter regions of MT genes from all three species were assessed for their ability to enhance transcription in response to the heavy metals Zn, Cd and Cu. The polymerase chain reaction was used to produce nested deletion sets of each promoter region and these were cloned into the mammalian expression vector pGL-2 upstream of the firefly luciferase gene. The inducibility of the different constructs in response to heavy metal challenge was tested in two cell lines, one fish cell line (homologous to rainbow trout and heterologous to the two other species), the rainbow trout hepatoma, RTH-149, cell line and one cell line that was heterologous to all studied species, the human hepatoblastoma; HepG2, cell line. Maximum inducibility of each gene was achieved with constructs containing both the proximal and the distal MRE clusters. Both the rainbow trout and the stone loach MT genes showed inducibility of comparable amplitude whilst the pike MT gene on the other hand was less inducible, partly due to fewer MREs and partly due to the TTTA box. These data indicate that more than one mechanism is responsible for the differences in cadmium sensitivity of these three teleost species. Although MT is the main heavy-metal detoxifying system in most vertebrates and appears to be contributing to the differences seen between rainbow trout and pike, the present study shows that the relative sensitivity of these species is not primarily due to MT.

Animals↗

PubMed1996

Phenobarbital induction of CYP1A1 gene expression in a primary culture of rainbow trout hepatocytes.

In mammals, phenobarbital (PB) is an in vivo inducer of the cytochrome P4502B (CYP2B) family, whereas in teleosts PB induction of cytochrome P450 is unclear. We show that teleost cytochrome P4502K1 (CYP2K1) protein levels and 7-pentoxyresorufin-O-deethylase activity were not induced by exposure of primary cultures of rainbow trout hepatocytes to PB. Instead, cytochrome P4501A1 (CYP1A1) gene expression was strongly induced by PB, based upon observations of marked increases in CYP1A1 mRNA, CYP1A1 protein, and 7-ethoxyresorufin-O-deethylase activity. In accordance with these data we provide a temporal study employing antibodies for the aromatic hydrocarbon (Ah) receptor that showed an increase in Ah receptor in nuclear extracts prepared from cells exposed to PB. Employment of the electrophoretic mobility shift assay (EMSA) showed PB to cause activation or "transformation" of the Ah receptor in nuclear extracts. Studies employing actinomycin D and cycloheximide indicated that PB induction of CYP1A1 was regulated at both the transcriptional and post-transcriptional levels. Nuclear run-off experiments confirm that PB causes an increase in CYP1A1 transcription. Inhibition of protein synthesis led to the superinduction of CYP1A1 mRNA, suggesting the regulation of teleost CYP1A1 may involve a labile repressor protein. These findings suggest that PB induction of the CYP1A1 gene involves the Ah receptor and is via transcriptional activation.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1995

Structural and functional analysis of the rainbow trout (Oncorhyncus mykiss) metallothionein-A gene.

In the present study, the distal part of the 5'-flanking region of the rainbow trout metallothionein-A promoter was sequenced in order to identify cis-acting regulatory elements. Analysis of this sequence combined with that previously reported for the 5'-flanking region directly proximal to the start of transcription revealed several putative regulatory sequences. In total, six metal-responsive elements (MREs) were identified; these sequences were organised into two clusters, one containing two copies of MRE and located close to the predicted TATA box sequence, and a second consisting of four MREs and lying 500-700 bp upstream from the start of transcription. In addition, the 5'-flanking region contained sequences sharing high similarity with the activator protein 1 consensus sequence as well as one nuclear-factor-interleukin-6-responsive element. Functional analysis of the promoter was performed by introducing deletion mutants of the 5'-flanking region into the vector pGL-2, directly upstream from the luciferase reporter gene. Both MRE clusters were needed for maximal metal inducibility in both rainbow trout hepatoma (RTH-149) and human hepatoblastoma (Hep G2) cell lines. Furthermore, the distal region was found to be functional in promoting gene transcription following exposure of RTH-149 cells to hydrogen peroxide.

Amino Acid Sequence↗

PubMed1995

Interaction of cadmium and oestradiol-17 beta on metallothionein and vitellogenin synthesis in rainbow trout (Oncorhynchus mykiss).

The induction of metallothionein and vitellogenin synthesis in rainbow trout liver was studied after injection of oestradiol-17 beta alone or in combination with cadmium or zinc. Intraperitoneal injection of oestradiol-17 beta increased the liver somatic index, with subsequent induction of vitellogenin synthesis. Oestradiol-17 beta did not induce metallothionein synthesis. Injection of cadmium induced the synthesis of metallothionein mRNA and metallothionein. Injection of oestradiol-17 beta in combination with cadmium resulted in inhibition of transcription and translation of both vitellogenin and metallothionein. Chromatography of liver cytosols revealed that cadmium, when co-injected with oestradiol-17 beta, did not bind to metallothionein but would initially bind to high-molecular-mass (HMr) cytosolic proteins. In fish injected with cadmium in combination with oestradiol-17 beta, cadmium was gradually redistributed from HMr proteins to metallothionein. This resulted in induction of metallothionein synthesis and in binding of most of the cadmium to metallothionein. Induction of vitellogenin mRNA was observed 15 days after injection, as cadmium was being redistributed to newly synthesized metallothionein. These findings indicate that cadmium inhibits the transcription of vitellogenin. The binding of cadmium to these non-metallothionein proteins represses the induction of metallothionein and results in increased toxicity of the metal. Preinduction of metallothionein by zinc injections resulted in decreased cadmium sensitivity of the fish and a decrease in the repression of vitellogenin mRNA. Furthermore, a role for metallothionein in the detoxification of cadmium is indicated by the induction of vitellogenin synthesis that occurs once metallothionein has begun sequestering cadmium.

Animals↗