Xiaomei Su

Microcystin-LR induced thyroid dysfunction and metabolic disorders in mice

There is growing evidence that microcystins (MCs) act as hazardous materials and can disrupt the endocrine systems of animals. However, the response of thyroid function and the related energy metabolism following MCs exposure is still unknown. In the present study, mice were injected intraperitoneally (i.p.) with doses of either 5 or 20 μg/kg MC-LR for 4 weeks. We report, for the first time, that mice exposed to 20 μg/kg MC-LR showed disrupted glucose, triglyceride and cholesterol metabolism with obvious symptoms of hyperphagia, polydipsia, and weight loss. The circulating thyroid hormone (TH) levels in mice following MC-LR exposure were detected. Significantly increased free triiodothyronine (FT3) and decreased free thyroxin (FT4) were largely responsible for the physiological aberrations and metabolic disorders observed in mice after the 20 μg/kg MC-LR exposure. Increased expression of TH receptor (Trα) and mTOR expression in the brain after the 20 μg/kg MC-LR exposure suggests that the increased FT3 enhanced mTOR signaling subsequently led to hyperphagia and elevated energy expenditure in mice. Furthermore, several genes involved in glucose homeostasis and lipid metabolism, which have been identified affected by TH, were also differentially expressed after MC-LR exposure. The above results clearly showed that mice exposed to MC-LR experienced thyroid dysfunction and its downstream functional changes, and are useful to better understand the endocrine toxicity of MC-LR to mammals or even humans.

First Identification of the Toxicity of Microcystins on Pancreatic Islet Function in Humans and the Involved Potential Biomarkers

Microcystins (MCs) produced by cyanobacteria have been recognized as a major public health threat. However, the toxicity of MCs to humans is still largely unknown. In this study, we examined the changes in pancreatic islet function in fishers exposed to ambient levels of MCs at Lake Taihu and, using a mouse model, explored the molecular mechanisms involved in toxicity. MCs content in the serum of fishers tested positive, with a range from 0.10 to 0.64 μg/L. Both lower blood insulin levels (2.26 ± 0.96 μIU/mL) and impaired fasting glucose were found in participants from the Meiliang Bay area in Lake Taihu, where MC-LR levels were substantially greater than the MC threshold established by WHO for drinking water. Animal experiments showed that glucose level increased by 27.9% in mice exposed to 5 μg/kg bw and decreased by 41.5% in mice exposed to 20 μg/kg bw. Blood insulin levels declined by 21.9% and 56.2% in mice exposed to 5 and 20 μg/kg bw MC-LR, respectively, which was consistent with the results observed in fishers. Furthermore, the diabetes gene pdx1 and several other proteins (such as Ppp3ca, Ide, Marcks, Pgk1, Suclg1, Ndufs4) involved in insulin secretion were identified for the first time in mice following MC-LR exposure; these biomarkers were considered responsible for MC-LR induced islet dysfunction. This study suggests that subchronic exposure to environmental levels of MCs may increase the risk of the occurrence of diabetes in humans.

Spatiotemporal Dynamics of Microcystin Variants and Relationships with Environmental Parameters in Lake Taihu, China

Excessive anthropogenically-caused nutrient loading from both external and internal sources has promoted the growth of cyanobacteria in Lake Taihu from 2005 to 2014, suggesting increased production and release of cyanotoxins. In order to explain the spatial distribution and temporal variation of microcystins (MCs), the intracellular concentrations of MCs (MC-LR, -RR and -YR, L, R and Y are abbreviations of leucine, arginine and tyrosine) were monitored monthly from July 2013 to June 2014. Three MC variants are present simultaneously in Lake Taihu; the MC-LR and -RR variants were dominant (accounting for 40% and 39% of the total), followed by MC-YR (21%). However, MC-YR accounted for a higher proportion in colder months, especially in March. The highest concentrations of intracellular MCs were found in July and October when cyanobacteria cell density also reached the maximum. The average concentrations of MC-LR, -RR and -YR in July were 4.69, 4.23 and 2.01 μg/L, respectively. In terms of the entire lake, toxin concentrations in northern parts were significantly higher than the eastern part in summer, when MC concentrations were several times higher than the guideline value by WHO throughout much of Lake Taihu. Results from correlation and redundancy analysis (RDA) showed that total MCs, including all variants, were strongly and positively correlated with cyanobacteria cell density, water temperature, total phosphorus (TP) and pH, whereas each variant had different correlation coefficients with each of the considered environmental variables. MC-RR showed a stronger relationship with temperature, in contrast to MC-YR and -LR. Dissolved inorganic carbon (DIC) showed a negative relationship with each variant, suggesting that rising DIC concentrations may inhibit cyanobacterial growth and thereby reduce MC production in the future.

Temporal patterns of phyto- and bacterioplankton and their relationships with environmental factors in Lake Taihu, China

Phytoplankton and bacterioplankton are integral components of aquatic food webs and play essential roles in the structure and function of freshwater ecosystems. However, little is known about how phyto- and bacterioplankton may respond synchronously to changing environmental conditions. Thus, we analyzed simultaneously the composition and structure of phyto- and bacterioplankton on a monthly basis over 12 months in cyanobacteria-dominated areas of Lake Taihu and compared their responses to changes in environmental factors. Metric multi-dimensional scaling (mMDS) revealed that the temporal variations of phyto- and bacterioplankton were significant. Time lag analysis (TLA) indicated that the temporal pattern of phytoplankton tended to exhibit convergent dynamics while bacterioplankton showed highly stable or stochastic variation. A significant directional change was found for bacterioplankton at the genus level and the slopes (rate of change) and regression R2 (low stochasticity or stability) were greater if Cyanobacteria were included, suggesting a higher level of instability in the bacterial community at lower taxonomy level. Consequently, phytoplankton responded more rapidly to the change in environmental conditions than bacterioplankton when analyzed at the phylum level, while bacterioplankton were more sensitive at the finer taxonomic resolution in Lake Taihu. Redundancy analysis (RDA) results showed that environmental variables collectively explained 51.0% variance of phytoplankton and 46.7% variance of bacterioplankton, suggesting that environmental conditions have a significant influence on the temporal variations of phyto- and bacterioplankton. Furthermore, variance partitioning indicated that the bacterial community structure was largely explained by water temperature and nitrogen, suggesting that these factors were the primary drivers shaping bacterioplankton.

Microcystin-LR induces dysfunction of insulin secretion in rat insulinoma (INS-1) cells: Implications for diabetes mellitus

Microcystins (MCs) are the most frequent cyanobacterial toxins observed in freshwater systems. Accumulating evidence suggests that MCs pose a serious threat to public health. However, the contributions of the exposure of MCs to the occurrence of human diseases remain largely unknown. This study provides the evidence of the effects of MC-LR on pancreatic β-cell function through the exposure of rat insulinoma (INS-1) cells to 0, 10, 20, or 40μM MC-LR for 72h and explores the underlying molecular mechanisms. Our results demonstrate that exposure to MC-LR for 72h suppresses cell viability, disturbs glucose-stimulated insulin secretion (GSIS), and decreases the expression of insulin protein. Moreover, MC-LR disrupts the cell cycle distribution and increases cell apoptosis at 20 or 40μM for 72h, respectively, indicating that the β-cell mass would be decreased by MC-LR exposure. A transcriptomic analysis revealed several key genes (e.g., Pdx-1, Neurod1, and Abcc8) involved in insulin secretion are significantly differentially expressed in INS-1 cells in response to MC-LR exposure. In addition, several signal transduction pathways associated with diabetes (e.g., type 1 and 2 diabetes) were also identified compared with the control cells. We recommend that MC be considered as a new environmental factor that promotes diabetes development. The identified key genes or pathways may potentially contribute to the future therapies in the environmental contaminants induced β-cell damage.

Accumulation of microcystins in a dominant Chironomid Larvae ( Tanypus chinensis ) of a large, shallow and eutrophic Chinese lake, Lake Taihu

Although there have been numerous studies on microcystin (MC) accumulation in aquatic organisms recently, the bioaccumulation of MCs in relatively small sized organisms, as well as potential influencing factors, has been rarely studied. Thus, in this study, we investigated the bioaccumulation of three MC congeners (-LR, -RR and -YR) in the chironomid larvae of Tanypus chinensis (an excellent food source for certain fishes), the potential sources of these MCs, and potentially relevant environmental parameters over the course of one year in Lake Taihu, China. MC concentrations in T. chinensis varied temporally with highest concentrations during the warmest months (except August 2013) and very low concentrations during the remaining months. Among the three potential MC sources, only intracellular MCs were significantly and positively correlated with MCs in T. chinensis. Although MC concentrations in T. chinensis significantly correlated with a series of physicochemical parameters of water column, cyanobacteria species explained the most variability of MC accumulation, with the rest primarily explained by extraMC-LR. These results indicated that ingestion of MC-producing algae of cyanobacteria accounted for most of the MC that accumulated in T. chinensis. The high MC concentrations in T. chinensis may pose a potential health threat to humans through trophic transfer.

Response of bacterial communities to cyanobacterial harmful algal blooms in Lake Taihu, China

Cyanobacterial harmful algal blooms are prevalent around the world, influencing aquatic organisms and altering the physico-chemical properties in freshwater systems. However, the response of bacterial communities to toxic cyanobacterial blooms and associated microcystins (MC) remain poorly understood even though global concentrations of MC have increased dramatically in the past few decades. To address this issue, the dynamics of bacterial community composition (BCC) in the water column and how BCC is influenced by both harmful cyanobacterial blooms and environmental factors were investigated on a monthly basis from August 2013 to July 2014 in Lake Taihu, China. Non-metric multidimensional scaling (NMDS) revealed that seasonal variation in BCC was significant, and that the succession of BCC greatly depends on changes in environmental conditions. Redundancy analysis (RDA) results showed that the overall variation of BCC was explained mainly by dissolved oxygen (DO), nitrate nitrogen (NO3--N), and Microcystis. The alpha biodiversity of the bacterial community was different among months with the highest diversity in February and the lowest diversity in October. Furthermore, significant negative relationships were found between alpha biodiversity indices and Microcystis abundance as well as with intracellular MC concentrations, indicating that Microcystis and associated MC may influence the bacterial community structure by reducing its biodiversity. This study shows that potential associations exist between toxic cyanobacterial blooms and bacterial communities but more investigations are needed to obtain a mechanistic understanding of their complex relationships.