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Bernardo Gonzalez - One of the best experts on this subject based on the ideXlab platform.
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Genomic analysis of the potential for aromatic compounds biodegradation in Burkholderiales.
Environmental microbiology, 2011Co-Authors: Danilo Pérez-pantoja, Dietmar H Pieper, Raúl Donoso, Loreine Agulló, Macarena Córdova, Michael Seeger, Bernardo GonzalezAbstract:The relevance of the β-proteobacterial Burkholderiales order in the degradation of a vast array of aromatic compounds, including several priority pollutants, has been largely assumed. In this review, the presence and organization of genes encoding oxygenases involved in aromatics biodegradation in 80 Burkholderiales genomes is analysed. This genomic analysis underscores the impressive Catabolic potential of this bacterial lineage, comprising nearly all of the central ring-cleavage pathways reported so far in bacteria and most of the peripheral pathways involved in channelling of a broad diversity of aromatic compounds. The more widespread pathways in Burkholderiales include protocatechuate ortho ring-cleavage, catechol ortho ring-cleavage, homogentisate ring-cleavage and phenylacetyl-CoA ring-cleavage pathways found in at least 60% of genomes analysed. In general, a genus-specific pattern of positional ordering of biodegradative genes is observed in the Catabolic clusters of these pathways indicating recent events in its evolutionary history. In addition, a significant bias towards secondary chromosomes, now termed chromids, is observed in the distribution of Catabolic genes across multipartite genomes, which is consistent with a genus-specific character. Strains isolated from environmental sources such as soil, rhizosphere, sediment or sludge show a higher content of Catabolic genes in their genomes compared with strains isolated from human, animal or plant hosts, but no significant difference is found among Alcaligenaceae, Burkholderiaceae and Comamonadaceae families, indicating that habitat is more of a determinant than phylogenetic origin in shaping aromatic Catabolic versatility.
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metabolic reconstruction of aromatic compounds degradation from the genome of the amazing pollutant degrading bacterium cupriavidus necator jmp134
Fems Microbiology Reviews, 2008Co-Authors: Danilo Perezpantoja, Rodrigo De La Iglesia, Dietmar H Pieper, Bernardo GonzalezAbstract:Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the Catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those Catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator : the β-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the Catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of Catabolic genes.
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metabolic reconstruction of aromatic compounds degradation from the genome of the amazing pollutant degrading bacterium cupriavidus necator jmp134
Fems Microbiology Reviews, 2008Co-Authors: Danilo Perezpantoja, Rodrigo De La Iglesia, Dietmar H Pieper, Bernardo GonzalezAbstract:Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the Catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those Catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator: the beta-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the Catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of Catabolic genes.
Dietmar H Pieper - One of the best experts on this subject based on the ideXlab platform.
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analysis of the microbial gene landscape and transcriptome for aromatic pollutants and alkane degradation using a novel internally calibrated microarray system
Environmental Microbiology, 2013Co-Authors: Ramiro Vilchezvargas, Robert Geffers, Maria Suarezdiez, Ianina Conte, Agnes Waliczek, Vanessa Sabrina Kaser, Monika Kralova, Howard Junca, Dietmar H PieperAbstract:Summary Despite various efforts to develop tools to detect and compare the Catabolic potential and activity for pollutant degradation in environmental samples, there is still a need for an open-source, curated and reliable array method. We developed a custom array system including a novel normalization strategy that can be applied to any microarray design, allowing the calculation of the reliability of signals and make cross-experimental comparisons. Array probes, which are fully available to the scientific community, were designed from knowledge-based curated databases for key aromatic Catabolic gene families and key alkane degradation genes. This design assigns signals to the respective protein subfamilies, thus directly inferring function and substrate specificity. Experimental procedures were optimized using DNA of four genome sequenced biodegradation strains and reliability of signals assessed through a novel normalization procedure, where a plasmid containing four artificial targets in increased copy numbers and co-amplified with the environmental DNA served as an internal calibration curve. The array system was applied to assess the Catabolic gene landscape and transcriptome of aromatic contaminated environmental samples, confirming the abundance of Catabolic gene subfamilies previously detected by functional metagenomics but also revealing the presence of previously undetected Catabolic groups and specifically their expression under pollutant stress.
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Genomic analysis of the potential for aromatic compounds biodegradation in Burkholderiales.
Environmental microbiology, 2011Co-Authors: Danilo Pérez-pantoja, Dietmar H Pieper, Raúl Donoso, Loreine Agulló, Macarena Córdova, Michael Seeger, Bernardo GonzalezAbstract:The relevance of the β-proteobacterial Burkholderiales order in the degradation of a vast array of aromatic compounds, including several priority pollutants, has been largely assumed. In this review, the presence and organization of genes encoding oxygenases involved in aromatics biodegradation in 80 Burkholderiales genomes is analysed. This genomic analysis underscores the impressive Catabolic potential of this bacterial lineage, comprising nearly all of the central ring-cleavage pathways reported so far in bacteria and most of the peripheral pathways involved in channelling of a broad diversity of aromatic compounds. The more widespread pathways in Burkholderiales include protocatechuate ortho ring-cleavage, catechol ortho ring-cleavage, homogentisate ring-cleavage and phenylacetyl-CoA ring-cleavage pathways found in at least 60% of genomes analysed. In general, a genus-specific pattern of positional ordering of biodegradative genes is observed in the Catabolic clusters of these pathways indicating recent events in its evolutionary history. In addition, a significant bias towards secondary chromosomes, now termed chromids, is observed in the distribution of Catabolic genes across multipartite genomes, which is consistent with a genus-specific character. Strains isolated from environmental sources such as soil, rhizosphere, sediment or sludge show a higher content of Catabolic genes in their genomes compared with strains isolated from human, animal or plant hosts, but no significant difference is found among Alcaligenaceae, Burkholderiaceae and Comamonadaceae families, indicating that habitat is more of a determinant than phylogenetic origin in shaping aromatic Catabolic versatility.
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metabolic reconstruction of aromatic compounds degradation from the genome of the amazing pollutant degrading bacterium cupriavidus necator jmp134
Fems Microbiology Reviews, 2008Co-Authors: Danilo Perezpantoja, Rodrigo De La Iglesia, Dietmar H Pieper, Bernardo GonzalezAbstract:Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the Catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those Catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator : the β-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the Catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of Catabolic genes.
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metabolic reconstruction of aromatic compounds degradation from the genome of the amazing pollutant degrading bacterium cupriavidus necator jmp134
Fems Microbiology Reviews, 2008Co-Authors: Danilo Perezpantoja, Rodrigo De La Iglesia, Dietmar H Pieper, Bernardo GonzalezAbstract:Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the Catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those Catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator: the beta-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the Catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of Catabolic genes.
Danilo Perezpantoja - One of the best experts on this subject based on the ideXlab platform.
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metabolic reconstruction of aromatic compounds degradation from the genome of the amazing pollutant degrading bacterium cupriavidus necator jmp134
Fems Microbiology Reviews, 2008Co-Authors: Danilo Perezpantoja, Rodrigo De La Iglesia, Dietmar H Pieper, Bernardo GonzalezAbstract:Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the Catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those Catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator : the β-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the Catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of Catabolic genes.
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metabolic reconstruction of aromatic compounds degradation from the genome of the amazing pollutant degrading bacterium cupriavidus necator jmp134
Fems Microbiology Reviews, 2008Co-Authors: Danilo Perezpantoja, Rodrigo De La Iglesia, Dietmar H Pieper, Bernardo GonzalezAbstract:Cupriavidus necator JMP134 is a model for chloroaromatics biodegradation, capable of mineralizing 2,4-D, halobenzoates, chlorophenols and nitrophenols, among other aromatic compounds. We performed the metabolic reconstruction of aromatics degradation, linking the Catabolic abilities predicted in silico from the complete genome sequence with the range of compounds that support growth of this bacterium. Of the 140 aromatic compounds tested, 60 serve as a sole carbon and energy source for this strain, strongly correlating with those Catabolic abilities predicted from genomic data. Almost all the main ring-cleavage pathways for aromatic compounds are found in C. necator: the beta-ketoadipate pathway, with its catechol, chlorocatechol, methylcatechol and protocatechuate ortho ring-cleavage branches; the (methyl)catechol meta ring-cleavage pathway; the gentisate pathway; the homogentisate pathway; the 2,3-dihydroxyphenylpropionate pathway; the (chloro)hydroxyquinol pathway; the (amino)hydroquinone pathway; the phenylacetyl-CoA pathway; the 2-aminobenzoyl-CoA pathway; the benzoyl-CoA pathway and the 3-hydroxyanthranilate pathway. A broad spectrum of peripheral reactions channel substituted aromatics into these ring cleavage pathways. Gene redundancy seems to play a significant role in the Catabolic potential of this bacterium. The literature on the biochemistry and genetics of aromatic compounds degradation is reviewed based on the genomic data. The findings on aromatic compounds biodegradation in C. necator reviewed here can easily be extrapolated to other environmentally relevant bacteria, whose genomes also possess a significant proportion of Catabolic genes.
Dirk Springael - One of the best experts on this subject based on the ideXlab platform.
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comparative genomics suggests mechanisms of genetic adaptation toward the catabolism of the phenylurea herbicide linuron in variovorax
Genome Biology and Evolution, 2020Co-Authors: Basak Ozturk, Johannes Werner, Jan P Meierkolthoff, Boyke Bunk, Cathrin Sproer, Dirk SpringaelAbstract:Biodegradation of the phenylurea herbicide linuron appears a specialization within a specific clade of the Variovorax genus. The linuron Catabolic ability is likely acquired by horizontal gene transfer but the mechanisms involved are not known. The full-genome sequences of six linuron-degrading Variovorax strains isolated from geographically distant locations were analyzed to acquire insight into the mechanisms of genetic adaptation toward linuron metabolism. Whole-genome sequence analysis confirmed the phylogenetic position of the linuron degraders in a separate clade within Variovorax and indicated that they unlikely originate from a common ancestral linuron degrader. The linuron degraders differentiated from Variovorax strains that do not degrade linuron by the presence of multiple plasmids of 20-839 kb, including plasmids of unknown plasmid groups. The linuron Catabolic gene clusters showed 1) high conservation and synteny and 2) strain-dependent distribution among the different plasmids. Most of them were bordered by IS1071 elements forming composite transposon structures, often in a multimeric array configuration, appointing IS1071 as a key element in the recruitment of linuron Catabolic genes in Variovorax. Most of the strains carried at least one (Catabolic) broad host range plasmid that might have been a second instrument for Catabolic gene acquisition. We conclude that clade 1 Variovorax strains, despite their different geographical origin, made use of a limited genetic repertoire regarding both Catabolic functions and vehicles to acquire linuron biodegradation.
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comparative genomics unravels mechanisms of genetic adaptation for the catabolism of the phenylurea herbicide linuron in variovorax
bioRxiv, 2019Co-Authors: Basak Ozturk, Johannes Werner, Jan P Meierkolthoff, Boyke Bunk, Cathrin Sproer, Dirk SpringaelAbstract:Abstract Biodegradation of the phenylurea herbicide linuron appears a specialization within a specific clade of the Variovorax genus. The linuron Catabolic ability is likely acquired by horizontal gene transfer but the mechanisms involved are not known. The full genome sequences of six linuron degrading Variovorax strains isolated from geographically distant locations were analyzed to acquire insight in the mechanisms of genetic adaptation towards linuron metabolism in Variovorax. Whole genome sequence analysis confirmed the phylogenetic position of the linuron degraders in a separate clade within Variovorax and indicated their unlikely origin from a common ancestral linuron degrader. The linuron degraders differentiated from non-degraders by the presence of multiple plasmids of 20 to 839 kb, including plasmids of unknown plasmid groups. The linuron Catabolic gene clusters showed (i) high conservation and synteny and (ii) strain-dependent distribution among the different plasmids. All were bordered by IS1071 elements forming composite transposon structures appointing IS1071 as key for Catabolic gene recruitment. Most of the strain carried at least one broad host range plasmid that might have been a second instrument for Catabolic gene acquisition. We conclude that clade 1Variovorax strains, despite their different geographical origin, made use of a limited genetic repertoire to acquire linuron biodegradation. Importance The genus Variovorax and especially a clade of strains that phylogenetically separates from the majority of Variovorax species, appears to be a specialist in the biodegradation of the phenyl urea herbicide linuron. Horizontal gene transfer (HGT) likely played an essential role in the genetic adaptation of those strain to acquire the linuron Catabolic genotype. However, we do not know the genetic repertoire involved in this adaptation both regarding Catabolic gene functions as well as gene functions that promote HGT neither do we know how this varies between the different strains. These questions are addressed in this paper by analyzing the full genome sequences of six linuron degrading Variovorax strains. This knowledge is important for understanding the mechanisms that steer world-wide genetic adaptation in a particular species and this for a particular phenotypic trait as linuron biodegradation.
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horizontal gene transfer and microbial adaptation to xenobiotics new types of mobile genetic elements and lessons from ecological studies
Trends in Microbiology, 2004Co-Authors: Dirk SpringaelAbstract:Abstract The characterization of bacteria that degrade organic xenobiotics has revealed that they can adapt to these compounds by expressing ‘novel' Catabolic pathways. At least some of them appear to have evolved by patchwork assembly of horizontally transmitted genes and subsequent mutations and gene rearrangements. Recent studies have revealed the existence of new types of xenobiotic Catabolic mobile genetic elements, such as Catabolic genomic islands, which integrate into the chromosome after transfer. The significance of horizontal gene transfer and patchwork assembly for bacterial adaptation to pollutants under real environmental conditions remains uncertain, but recent publications suggest that these processes do occur in a polluted environment.
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the role of mobile genetic elements in bacterial adaptation to xenobiotic organic compounds
Current Opinion in Biotechnology, 2003Co-Authors: Eva M. Top, Dirk SpringaelAbstract:Retrospective studies clearly indicate that mobile genetic elements (MGEs) play a major role in the in situ spread and even de novo construction of Catabolic pathways in bacteria, allowing bacterial communities to rapidly adapt to new xenobiotics. The construction of novel pathways seems to occur by an assembly process that involves horizontal gene transfer: different appropriate genes or gene modules that encode different parts of the novel pathway are recruited from phylogenetically related or distant hosts into one single host. Direct evidence for the importance of Catabolic MGEs in bacterial adaptation to xenobiotics stems from observed correlations between Catabolic gene transfer and accelerated biodegradation in several habitats and from studies that monitor Catabolic MGEs in polluted sites.
Jae-sung Kim - One of the best experts on this subject based on the ideXlab platform.
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coumestrol counteracts interleukin 1β induced Catabolic effects by suppressing inflammation in primary rat chondrocytes
Inflammation, 2017Co-Authors: Jaeseek You, Ina Cho, Kyeongrok Kang, Gyeongje Lee, Yoseob Seo, Sugwan Kim, Chun Sung Kim, Do Kyung Kim, Jae-sung KimAbstract:In the present study, we investigated the anti-Catabolic effects of coumestrol, a phytoestrogen derived from herbal plants, against interleukin-1β-induced cartilage degeneration in primary rat chondrocytes and articular cartilage. Coumestrol did not affect the viability of human normal oral keratinocytes and primary rat chondrocytes treated for 24 h and 21 days, respectively. Although coumestrol did not significantly increase the proteoglycan contents in long-term culture, it abolished the interleukin-1β-induced loss of proteoglycans in primary rat chondrocytes and knee articular cartilage. Furthermore, coumestrol suppressed the expression of matrix-degrading enzymes such as matrix metalloproteinase-13, −3, and −1 in primary rat chondrocytes stimulated with interleukin-1β. Moreover, the expression of Catabolic factors such as nitric oxide synthase, cyclooxygenase-2, prostaglandin E2, and inflammatory cytokines in interleukin-1β-stimulated primary rat chondrocytes was suppressed by coumestrol. In summary, these results indicate that coumestrol counteracts the Catabolic effects induced by interleukin-1β through the suppression of inflammation. Therefore, based on its biological activity and safety profile, coumestrol could be used as a potential anti-Catabolic biomaterial for osteoarthritis.
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lactoferricin mediates anti inflammatory and anti Catabolic effects via inhibition of il 1 and lps activity in the intervertebral disc
Journal of Cellular Physiology, 2013Co-Authors: Jae-sung Kim, Michael B. Ellman, Dongyao Yan, David W Hoskin, Di Chen, Guozhi Xiao, Gabriella Csszabo, Doug D Buechter, Andre J Van WijnenAbstract:The Catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-Catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated Catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes Catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the Catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future.
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lactoferricin mediates anabolic and anti Catabolic effects in the intervertebral disc
Journal of Cellular Physiology, 2012Co-Authors: Jae-sung Kim, Michael B. Ellman, Dongyao Yan, Andre J Van Wijnen, Gillian Murphy, David W HoskinAbstract:Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and Catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated Catabolic enzymes. LfcinB's anti-Catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-Catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future.