Toxic harmful algal blooms(HABs)can cause deleterious effects in marine organisms,threatening the stability of marine ecosystems.It is well known that different strains,natural populations and growth conditions of the...Toxic harmful algal blooms(HABs)can cause deleterious effects in marine organisms,threatening the stability of marine ecosystems.It is well known that different strains,natural populations and growth conditions of the same toxic algal species may lead to different amount of phycotoxin production and the ensuing toxicity.To fully assess the ecological risk of toxic HABs,it is of great importance to investigate the toxic effects of phycotoxins in marine organisms.In this study,the short-term toxicity of 14 common phycotoxins(alone and in combination)in the marine zooplankton Artemia salina was investigated.The 48 h LC_(50)of the 14 phycotoxins varied from 0.0193µg/mL to 2.415µg/mL.The most potent phycotoxin was azaspiracids-3(AZA3;with a LC_(50)of 0.0193µg/mL),followed by azaspiracids-2(AZA2;0.0226µg/mL),pectenotoxin-2(PTX2;0.0460µg/mL)and dinophysistoxin-1(DTX1;0.0818µg/mL).For the binary exposure,okadaic acid(OA)induced potential additive effects with DTX1,probably due to their similar structure(polyether fatty acid)and mode of action(attacking the serine/threonine phosphoprotein phosphatases).On the other hand,OA showed potential antagonistic effects with PTX2,which might be accounted for by their activation on the detoxification activity of cytochrome P450 activity.In addition,DTX1 induced potential synergetic effects with saxitoxin(STX),yessotoxin(YTX)or PTX2,suggesting the hazard potency of the mixtures of DTX1 and other phycotoxins(like STX,YTX and PTX2)with regard to the ecological risk.These results provide valuable toxicological data for assessing the impact of phycotoxins on marine planktonic species and highlight the potential ecological risk of toxic HABs in marine ecosystems.展开更多
Bromodomain-containing protein 7 (BRD7) has been shown to interact with the regulatory subunit of phosphatidylinositol 3-kinase(PI3K), p85, in the insulin signaling pathway. Here, we show that upregulation of hepatic ...Bromodomain-containing protein 7 (BRD7) has been shown to interact with the regulatory subunit of phosphatidylinositol 3-kinase(PI3K), p85, in the insulin signaling pathway. Here, we show that upregulation of hepatic BRD7 improves glucose homeostasiseven in the absence of either p85 isoform, p85a or p85b. However, BRD7 leads to differential activation of downstream effectorproteins in the insulin signaling pathway depending on which isoform of p85 is present. In the presence of only p85a, BRD7 overexpression increases phosphorylation of insulin receptor (IR) upon insulin stimulation, without increasing the recruitment of p85to IR substrate. Overexpression of BRD7 also increases activation of Akt in response to insulin, but does not affect basal phosphorylation levels of Akt. Meanwhile, the phosphorylation of glycogen synthase kinase 3b (GSK3b) is increased by overexpression ofBRD7. On the other hand, in the presence of only p85b, BRD7 overexpression does not affect phosphorylation levels of IR, and Aktphosphorylation is not affected by insulin stimulation following BRD7 upregulation. However, BRD7 overexpression leads to increased basal phosphorylation levels of Akt and GSK3b. These data demonstrate that BRD7’s action on glucose homeostasis doesnot require the presence of both p85 isoforms, and p85a and p85b have unique roles in insulin signaling in the liver.展开更多
基金The National Natural Science Foundation of China under contract No.41576120the Special Fund Project for Marine and Fishery Protection and Development in Fujian Province,China under contract No.FZJZ-2021-1the National Key R&D Program of China under contract No.2017YFC1404803.
文摘Toxic harmful algal blooms(HABs)can cause deleterious effects in marine organisms,threatening the stability of marine ecosystems.It is well known that different strains,natural populations and growth conditions of the same toxic algal species may lead to different amount of phycotoxin production and the ensuing toxicity.To fully assess the ecological risk of toxic HABs,it is of great importance to investigate the toxic effects of phycotoxins in marine organisms.In this study,the short-term toxicity of 14 common phycotoxins(alone and in combination)in the marine zooplankton Artemia salina was investigated.The 48 h LC_(50)of the 14 phycotoxins varied from 0.0193µg/mL to 2.415µg/mL.The most potent phycotoxin was azaspiracids-3(AZA3;with a LC_(50)of 0.0193µg/mL),followed by azaspiracids-2(AZA2;0.0226µg/mL),pectenotoxin-2(PTX2;0.0460µg/mL)and dinophysistoxin-1(DTX1;0.0818µg/mL).For the binary exposure,okadaic acid(OA)induced potential additive effects with DTX1,probably due to their similar structure(polyether fatty acid)and mode of action(attacking the serine/threonine phosphoprotein phosphatases).On the other hand,OA showed potential antagonistic effects with PTX2,which might be accounted for by their activation on the detoxification activity of cytochrome P450 activity.In addition,DTX1 induced potential synergetic effects with saxitoxin(STX),yessotoxin(YTX)or PTX2,suggesting the hazard potency of the mixtures of DTX1 and other phycotoxins(like STX,YTX and PTX2)with regard to the ecological risk.These results provide valuable toxicological data for assessing the impact of phycotoxins on marine planktonic species and highlight the potential ecological risk of toxic HABs in marine ecosystems.
基金This work was supported by the National Institutes of Health(R01DK118244)the American Heart Association(18IPA34140057)+1 种基金the American Diabetes Association(1-17-IBS-104)the faculty start up fund provided to S.W.P.from Boston Children’s Hospital.
文摘Bromodomain-containing protein 7 (BRD7) has been shown to interact with the regulatory subunit of phosphatidylinositol 3-kinase(PI3K), p85, in the insulin signaling pathway. Here, we show that upregulation of hepatic BRD7 improves glucose homeostasiseven in the absence of either p85 isoform, p85a or p85b. However, BRD7 leads to differential activation of downstream effectorproteins in the insulin signaling pathway depending on which isoform of p85 is present. In the presence of only p85a, BRD7 overexpression increases phosphorylation of insulin receptor (IR) upon insulin stimulation, without increasing the recruitment of p85to IR substrate. Overexpression of BRD7 also increases activation of Akt in response to insulin, but does not affect basal phosphorylation levels of Akt. Meanwhile, the phosphorylation of glycogen synthase kinase 3b (GSK3b) is increased by overexpression ofBRD7. On the other hand, in the presence of only p85b, BRD7 overexpression does not affect phosphorylation levels of IR, and Aktphosphorylation is not affected by insulin stimulation following BRD7 upregulation. However, BRD7 overexpression leads to increased basal phosphorylation levels of Akt and GSK3b. These data demonstrate that BRD7’s action on glucose homeostasis doesnot require the presence of both p85 isoforms, and p85a and p85b have unique roles in insulin signaling in the liver.