Potential for human exposure to Beta-N-methylamino-L-alanine in a freshwater system
- Authors: Scott, Laura Louise
- Date: 2014
- Subjects: Water quality biological assessment , Cyanobacteria , Neurotoxic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/5159 , vital:20816
- Description: β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid associated with human neurodegenerative diseases. The content of BMAA in cyanobacteria is modulated by nitrogen in laboratory cultures. In order to evaluate the potential for human exposure, the nitrogen modulation of BMAA content needed verification in a natural environment. In accordance with laboratory culture studies, data presented in this study show that combined nitrogen was the most significant modulator of both cellular microcystin (MC) and BMAA content in phytoplankton in an environmental cyanobacterial bloom. While BMAA is produced upon nitrogen deprivation, MC is only produced at a specific nitrogen threshold where the rate of increase of nitrogen in the cell exceeds the carbon fixation rate. As BMAA and MC were detected in phytoplankton sourced from the Hartbeespoort Dam reservoir, the transfer of these cyanotoxins to organisms of higher trophic levels was investigated. Both BMAA and MC were detected at high concentrations in the liver and muscle tissue of fish sourced from the Hartbeespoort Dam reservoir indicating that consumption of fish from this reservoir constitutes a serious risk of exposure to cyanotoxins. In addition to the dietary exposure route to BMAA, two recent studies reported a correlation between Amyotrophic Lateral Sclerosis (ALS) incidence and the potential for aerosol exposure to cyanobacteria. With the absence of any evidence of the systemic distribution of BMAA following inhalation, an evaluation of the potential exposure risk associated with living in close proximity to this reservoir was deemed premature. A laboratory experiment investigating the effect and systemic fate of inhaled aerosolised BMAA was therefore conducted in order to determine the feasibility of inhalation as a potential BMAA exposure route. Data from the rat inhalation exposure study, however, showed that in rats BMAA inhalation may not constitute a significant mechanism of toxicity at environmental BMAA levels.
- Full Text:
- Date Issued: 2014
- Authors: Scott, Laura Louise
- Date: 2014
- Subjects: Water quality biological assessment , Cyanobacteria , Neurotoxic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/5159 , vital:20816
- Description: β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid associated with human neurodegenerative diseases. The content of BMAA in cyanobacteria is modulated by nitrogen in laboratory cultures. In order to evaluate the potential for human exposure, the nitrogen modulation of BMAA content needed verification in a natural environment. In accordance with laboratory culture studies, data presented in this study show that combined nitrogen was the most significant modulator of both cellular microcystin (MC) and BMAA content in phytoplankton in an environmental cyanobacterial bloom. While BMAA is produced upon nitrogen deprivation, MC is only produced at a specific nitrogen threshold where the rate of increase of nitrogen in the cell exceeds the carbon fixation rate. As BMAA and MC were detected in phytoplankton sourced from the Hartbeespoort Dam reservoir, the transfer of these cyanotoxins to organisms of higher trophic levels was investigated. Both BMAA and MC were detected at high concentrations in the liver and muscle tissue of fish sourced from the Hartbeespoort Dam reservoir indicating that consumption of fish from this reservoir constitutes a serious risk of exposure to cyanotoxins. In addition to the dietary exposure route to BMAA, two recent studies reported a correlation between Amyotrophic Lateral Sclerosis (ALS) incidence and the potential for aerosol exposure to cyanobacteria. With the absence of any evidence of the systemic distribution of BMAA following inhalation, an evaluation of the potential exposure risk associated with living in close proximity to this reservoir was deemed premature. A laboratory experiment investigating the effect and systemic fate of inhaled aerosolised BMAA was therefore conducted in order to determine the feasibility of inhalation as a potential BMAA exposure route. Data from the rat inhalation exposure study, however, showed that in rats BMAA inhalation may not constitute a significant mechanism of toxicity at environmental BMAA levels.
- Full Text:
- Date Issued: 2014
In vivo and In vitro investigations to elucidate the associations of B-N-methylamino-L-alanine with proteins
- Authors: Van Onselen, Rianita
- Date: 2015
- Subjects: Cyanobacteria , Bioaccumulation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/4923 , vital:20767
- Description: The cyanobacterially synthesized non-canonical amino acid β-N-methylamino-ʟ-alanine (BMAA) has been proposed to be a causative agent in the development of sporadic neurodegenerative diseases. This neurotoxin bioaccumulates and biomagnifies with increasing trophic levels in ecosystems by associating with proteins. It has been suggested that these associations with host proteins also serve as a reservoir from where BMAA is slowly released with normal protein catabolism, resulting in a continuous low level exposure. However, the nature of these associations remains poorly defined. The widely accepted hypothesis regarding the nature of these associations is that BMAA associates with proteins through primary incorporation into proteins with specific replacement of serine. In addition to excitotoxicity, BMAA misincorporation has been proposed as a potential mechanism of toxicity because of its link to protein tangle diseases. Interactions between BMAA and proteins that are not the result of misincorporation, have also been observed. However, the nature of these non-primary associations has not been investigated. This study focussed on establishing whether BMAA is misincorporated into host proteins with consequent toxicity, and on elucidating the nature of the BMAA-protein associations not linked to primary incorporation. In comparative studies between BMAA and canavanine, an arginine analogue known to misincorporate, exposure to BMAA did not result in any toxicity in prokaryotes or in an undifferentiated eukaryotic mammalian cell line, in contrast to what was observed upon canavanine exposure. Differentiation of the cell line with nerve growth factor to express glutamate receptors resulted in marked toxicity upon BMAA exposure, highlighting excitoxicity as the main mechanism of BMAA toxicity. Furthermore, it was demonstrated that BMAA interacts with free amino acids and proteins in the absence of de novo protein synthesis, causing enzyme inhibition and protein misfolding. It was concluded that BMAA does not interact with proteins through primary incorporation and that the observed associations are the result of an interaction between BMAA and amino acid side chains to form covalent bonds.
- Full Text:
- Date Issued: 2015
- Authors: Van Onselen, Rianita
- Date: 2015
- Subjects: Cyanobacteria , Bioaccumulation
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/4923 , vital:20767
- Description: The cyanobacterially synthesized non-canonical amino acid β-N-methylamino-ʟ-alanine (BMAA) has been proposed to be a causative agent in the development of sporadic neurodegenerative diseases. This neurotoxin bioaccumulates and biomagnifies with increasing trophic levels in ecosystems by associating with proteins. It has been suggested that these associations with host proteins also serve as a reservoir from where BMAA is slowly released with normal protein catabolism, resulting in a continuous low level exposure. However, the nature of these associations remains poorly defined. The widely accepted hypothesis regarding the nature of these associations is that BMAA associates with proteins through primary incorporation into proteins with specific replacement of serine. In addition to excitotoxicity, BMAA misincorporation has been proposed as a potential mechanism of toxicity because of its link to protein tangle diseases. Interactions between BMAA and proteins that are not the result of misincorporation, have also been observed. However, the nature of these non-primary associations has not been investigated. This study focussed on establishing whether BMAA is misincorporated into host proteins with consequent toxicity, and on elucidating the nature of the BMAA-protein associations not linked to primary incorporation. In comparative studies between BMAA and canavanine, an arginine analogue known to misincorporate, exposure to BMAA did not result in any toxicity in prokaryotes or in an undifferentiated eukaryotic mammalian cell line, in contrast to what was observed upon canavanine exposure. Differentiation of the cell line with nerve growth factor to express glutamate receptors resulted in marked toxicity upon BMAA exposure, highlighting excitoxicity as the main mechanism of BMAA toxicity. Furthermore, it was demonstrated that BMAA interacts with free amino acids and proteins in the absence of de novo protein synthesis, causing enzyme inhibition and protein misfolding. It was concluded that BMAA does not interact with proteins through primary incorporation and that the observed associations are the result of an interaction between BMAA and amino acid side chains to form covalent bonds.
- Full Text:
- Date Issued: 2015
Bioaccumulation and ecotoxicology of b-methylamino-l-alanine (BMAA) in model crop plants
- Niyonzima, Francois Niyongabo
- Authors: Niyonzima, Francois Niyongabo
- Date: 2010
- Subjects: Cyanobacteria , Environmental toxicology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10312 , http://hdl.handle.net/10948/1475 , Cyanobacteria , Environmental toxicology
- Description: Cyanobacteria are known to produce a variety of toxic compounds. β-N-methylamino-L-alanine (BMAA) is one of the neurotoxins produced by most cyanobacteria. BMAA has been implicated in amyotrophic lateral sclerosis / Parkinsonism dementia complex (ALS / PDC) and was suggested to contribute to this pathology after biomagnification and slow release of BMAA from a protein associated form. The uptake and accumulation of BMAA by the aquatic macrophyte Ceratophyllum demersum has recently been shown, but the consumption of aquatic macrophytes by humans is not typical. The uptake by, and accumulation in, crop plants (Nasturtium officinale and Daucus carota) was therefore investigated so as to establish the existence of any risk to humans from the consumption of plants irrigated with water from dams with high cyanobacterial biomass and therefore high BMAA levels. After the exposure to the BMAA through the growth medium, BMAA had no effect on growth and development of N. officinale and D. carota. The uptake and bioaccumulation of BMAA was observed in N. officinale and D. carota, and was found to be concentration-dependent. Both free and bound cellular BMAA was detected following BMAA exposure through the growth medium. The photosynthetic apparatus of N. officinale was not significantly damaged. The uptake and accumulation of BMAA in edible terrestrial plants may constitute another route of human exposure to BMAA; it may now be prudent to avoid spray irrigation of edible plants with waters from dams with high cyanobacterial biomass and therefore high BMAA levels. After uptake by plants, the cyanotoxins may induce oxidative stress. A recent study showed that BMAA has a significant inhibitory effect on the oxidative stress enzymes in C. demersum. Therefore, the toxicological effects on selected plants were investigated by a range of biochemical enzyme assays in order to establish the plant stress response to exogenous BMAA. The inhibition of antioxidant enzymes upon exposure of N. officinale to BMAA through the growth medium was observed. The inhibition of antioxidant defence enzymes by BMAA correlated with the BMAA bioaccumulation in N. officinale. Further investigations are needed to analyze the uptake, accumulation, and ecotoxicology of BMAA in other crop plants, and to examine the fate of BMAA in these plants particularly its distribution and metabolism.
- Full Text:
- Date Issued: 2010
- Authors: Niyonzima, Francois Niyongabo
- Date: 2010
- Subjects: Cyanobacteria , Environmental toxicology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10312 , http://hdl.handle.net/10948/1475 , Cyanobacteria , Environmental toxicology
- Description: Cyanobacteria are known to produce a variety of toxic compounds. β-N-methylamino-L-alanine (BMAA) is one of the neurotoxins produced by most cyanobacteria. BMAA has been implicated in amyotrophic lateral sclerosis / Parkinsonism dementia complex (ALS / PDC) and was suggested to contribute to this pathology after biomagnification and slow release of BMAA from a protein associated form. The uptake and accumulation of BMAA by the aquatic macrophyte Ceratophyllum demersum has recently been shown, but the consumption of aquatic macrophytes by humans is not typical. The uptake by, and accumulation in, crop plants (Nasturtium officinale and Daucus carota) was therefore investigated so as to establish the existence of any risk to humans from the consumption of plants irrigated with water from dams with high cyanobacterial biomass and therefore high BMAA levels. After the exposure to the BMAA through the growth medium, BMAA had no effect on growth and development of N. officinale and D. carota. The uptake and bioaccumulation of BMAA was observed in N. officinale and D. carota, and was found to be concentration-dependent. Both free and bound cellular BMAA was detected following BMAA exposure through the growth medium. The photosynthetic apparatus of N. officinale was not significantly damaged. The uptake and accumulation of BMAA in edible terrestrial plants may constitute another route of human exposure to BMAA; it may now be prudent to avoid spray irrigation of edible plants with waters from dams with high cyanobacterial biomass and therefore high BMAA levels. After uptake by plants, the cyanotoxins may induce oxidative stress. A recent study showed that BMAA has a significant inhibitory effect on the oxidative stress enzymes in C. demersum. Therefore, the toxicological effects on selected plants were investigated by a range of biochemical enzyme assays in order to establish the plant stress response to exogenous BMAA. The inhibition of antioxidant enzymes upon exposure of N. officinale to BMAA through the growth medium was observed. The inhibition of antioxidant defence enzymes by BMAA correlated with the BMAA bioaccumulation in N. officinale. Further investigations are needed to analyze the uptake, accumulation, and ecotoxicology of BMAA in other crop plants, and to examine the fate of BMAA in these plants particularly its distribution and metabolism.
- Full Text:
- Date Issued: 2010
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