Science: targeting ASIC channel may reduce jaundice related nerve damage

February 17, 2020 / bioun / - - bilirubin (bilirubin) is the waste of heme metabolism of red blood cells in the blood, which is mainly converted from hemoglobin The life span of human red blood cells is generally 120 days After death, red blood cells become indirect bilirubin, which is transformed into direct bilirubin through the liver, forming bile, and then discharged into the bile duct, and finally discharged through the stool The sum of indirect bilirubin and direct bilirubin is total bilirubin If there is any obstacle in any of the above links, jaundice may occur When bilirubin exceeds the normal value, bilirubin is on the high side, which is hyperbilirubinemia When the total bilirubin is 34 μ mol / L, jaundice can be found clinically; if the total bilirubin in serum exceeds the normal range and jaundice cannot be seen by naked eyes, it is called recessive jaundice Jaundice is most common in hepatobiliary diseases, but other systemic diseases can also occur Neonatal hyperbilirubinemia, also known as jaundice, is a pediatric disease caused by high bilirubin level Jaundice can cause neurotoxicity and neurological dysfunction when accompanied by acidosis caused by infection, ischemia and hypoxia A popular view is that acidosis will increase the permeability of blood-brain barrier to bilirubin and increase its neurotoxicity In a new study, researchers from China's Shanghai Jiaotong University, Canada's Toronto Institute of sick children, the University of Toronto and Ukraine's National Academy of Sciences, bog Moretz Institute of physiology, studied the association between acidosis and jaundice in human samples and animal models, and found that compared with newborns with jaundice without acidosis, in newborns with acidosis And jaundiced newborns in the sample, neuron damage increased The relevant research results were published in the Journal of Science Translational Medicine on February 12, 2020 The title of the paper is "bilirubin enhancements the activity of ASIC channels to achieve neurotoxicity in national hyperbilirubinemia in mice" Bilirubin chemical structure formula They found that the increase of LDH in cerebrospinal fluid of infants with hyperbilirubinemia and acidosis was strongly correlated with the severity of acidosis, but not with the increase of bilirubin concentration Bilirubin shows limited toxicity in the newborn neurons of mice, but it can strongly enhance the activity of acid sensing ion channel (ASIC), which leads to the increase of intracellular calcium concentration and peak discharge, and leads to cell death In addition, hyperbilirubinemia and acidosis caused by hypoxia promote long-term impairment of learning, memory and complex sensory motor function in newborn mice, which can be greatly weakened by eliminating ASIC These findings suggest that targeting ASIC may reduce jaundice related neurological damage (BIOON Com) reference: Ke Lai et al Bilirubin enhances the activity of ASIC channels to exacherbat neurotoxicity in national hyperbilirubinemia in mice Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aax1337