With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nep...With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.展开更多
Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectiv...Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectively.They are expressed in many tissues,such as the liver and kidney,and mediate the absorption and excretion of many endogenous and exogenous substances,including various drugs.Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm.OATs and OATPs are abundantly expressed in the liver,where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs.However,differences in the locations of glycosylation sites,phosphorylation sites,and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver,which ultimately results in their different roles in the liver.To date,few articles have addressed these aspects of OAT and OATP structures,and we study further the similarities and differences in their structures,tissue distribution,substrates,and roles in liver diseases.展开更多
Aluminum(Al)is the most abundant metal element in the earth’s crust.On acid soils,at pH 5.5 or lower,part of insoluble Al-containing minerals become solubilized into soil solution,with resultant highly toxic effects ...Aluminum(Al)is the most abundant metal element in the earth’s crust.On acid soils,at pH 5.5 or lower,part of insoluble Al-containing minerals become solubilized into soil solution,with resultant highly toxic effects on plant growth and development.Nevertheless,some plants have developed Al-tolerance mechanisms that enable them to counteract this Al toxicity.One such well-documented mechanism is the Al-induced secretion of organic acid anions,including citrate,malate,and oxalate,from plant roots.Once secreted,these anions chelate external Al ions,thus protecting the secreting plant from Al toxicity.Genes encoding the citrate and malate transporters responsible for secretion have been identified and characterized,and accumulating evidence indicates that regulation of the expression of these transporter genes is critical for plant Al tolerance.In this review,we outline the recent history of research into plant Al-tolerance mechanisms,with special emphasis on the physiology of Al-induced secretion of organic acid anions from plant roots.In particular,we summarize the identification of genes encoding organic acid transporters and review current understanding of genes regulating organic acid secretion.We also discuss the possible signaling pathways regulating the expression of organic acid transporter genes.展开更多
基金National Natural Science Foundation of China(Nos.81673684,81703626,81573690)Double First-Class University projects(No.CPU2018GY33)。
文摘With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.
文摘Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectively.They are expressed in many tissues,such as the liver and kidney,and mediate the absorption and excretion of many endogenous and exogenous substances,including various drugs.Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm.OATs and OATPs are abundantly expressed in the liver,where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs.However,differences in the locations of glycosylation sites,phosphorylation sites,and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver,which ultimately results in their different roles in the liver.To date,few articles have addressed these aspects of OAT and OATP structures,and we study further the similarities and differences in their structures,tissue distribution,substrates,and roles in liver diseases.
基金supported by the National Natural Science Foundation of China(Nos.31572193,31760615,and 31760584)111 Project(No.B14027)the Changjiang Scholars Program of China
文摘Aluminum(Al)is the most abundant metal element in the earth’s crust.On acid soils,at pH 5.5 or lower,part of insoluble Al-containing minerals become solubilized into soil solution,with resultant highly toxic effects on plant growth and development.Nevertheless,some plants have developed Al-tolerance mechanisms that enable them to counteract this Al toxicity.One such well-documented mechanism is the Al-induced secretion of organic acid anions,including citrate,malate,and oxalate,from plant roots.Once secreted,these anions chelate external Al ions,thus protecting the secreting plant from Al toxicity.Genes encoding the citrate and malate transporters responsible for secretion have been identified and characterized,and accumulating evidence indicates that regulation of the expression of these transporter genes is critical for plant Al tolerance.In this review,we outline the recent history of research into plant Al-tolerance mechanisms,with special emphasis on the physiology of Al-induced secretion of organic acid anions from plant roots.In particular,we summarize the identification of genes encoding organic acid transporters and review current understanding of genes regulating organic acid secretion.We also discuss the possible signaling pathways regulating the expression of organic acid transporter genes.
