L-Theanine Protects against Methylglyoxal-Induced Oxidative Stress and Tight Junction Disruption in Human Cerebral Microvascular Endothelial Cells  

作　　者：Kohshi Kusumoto Kouyoh Habuchi Satoru Sakuma Keiichiro Okuhira Kohshi Kusumoto;Kouyoh Habuchi;Satoru Sakuma;Keiichiro Okuhira(Department of Environment and Health Sciences, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka, Japan)

机构地区：[1]Department of Environment and Health Sciences, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Osaka, Japan

出　　处：《Food and Nutrition Sciences》2024年第12期1218-1229,共12页食品与营养科学(英文)

摘　　要：The brain’s blood microvessels restrict the exchange of substances between the blood and brain tissue through the blood-brain barrier (BBB). Methyl-glyoxal (MG), a byproduct of glucose metabolism, contributes to the formation of advanced glycation end products (AGEs) and disrupts the BBB, which is associated with neurodegenerative diseases. L-Theanine (TA), an amino acid found in green tea with antioxidant properties, may protect the BBB. This study aimed to determine whether MG increases reactive oxygen species (ROS) and permeability by reducing tight junction proteins in human cerebral microvascular endothelial cells (hCMEC/d3), and whether TA pretreatment can counteract these effects. Our findings demonstrated that MG treatment led to increased BBB permeability, decreased transendothelial electrical resistance (TEER) values to 39% of control levels, reduced expression of Claudin-5 to 53% and Occludin to 69% of control levels, and elevated intracellular ROS levels. TA pretreatment restored barrier integrity, preserved tight junction protein expression, and decreased ROS accumulation to levels comparable to control levels. These findings suggest that TA effectively prevents MG-induced BBB dysfunction by reducing oxidative stress and maintaining tight junction proteins, showing promise as a protective agent for the BBB in conditions associated with elevated MG and AGEs.The brain’s blood microvessels restrict the exchange of substances between the blood and brain tissue through the blood-brain barrier (BBB). Methyl-glyoxal (MG), a byproduct of glucose metabolism, contributes to the formation of advanced glycation end products (AGEs) and disrupts the BBB, which is associated with neurodegenerative diseases. L-Theanine (TA), an amino acid found in green tea with antioxidant properties, may protect the BBB. This study aimed to determine whether MG increases reactive oxygen species (ROS) and permeability by reducing tight junction proteins in human cerebral microvascular endothelial cells (hCMEC/d3), and whether TA pretreatment can counteract these effects. Our findings demonstrated that MG treatment led to increased BBB permeability, decreased transendothelial electrical resistance (TEER) values to 39% of control levels, reduced expression of Claudin-5 to 53% and Occludin to 69% of control levels, and elevated intracellular ROS levels. TA pretreatment restored barrier integrity, preserved tight junction protein expression, and decreased ROS accumulation to levels comparable to control levels. These findings suggest that TA effectively prevents MG-induced BBB dysfunction by reducing oxidative stress and maintaining tight junction proteins, showing promise as a protective agent for the BBB in conditions associated with elevated MG and AGEs.

关 键 词：L-THEANINE METHYLGLYOXAL Oxidative Stress Tight Junction Blood-Brain Barrier 

分 类 号：X70[环境科学与工程—环境工程]