Adrenomedullin protects against hypoxia/reoxygenation-induced cell death by suppression of reactive oxygen species via thiol redox systems.
Adrenomedullin (ADM) functions as a survival factor against hypoxic cell death. However, molecular mechanisms underlying the cell survival pathway remain largely unknown. In this report, we showed that ADM suppressed reactive oxygen species (ROS) increase by inhibiting reduction of glutathione (GSH) level in hypoxia/reoxygenation (H/R) injury, and increased the activities of glutathione peroxidase and reductase. In addition, ADM maintained total and active reduced thioredoxin (Trx) levels against H/R. We also found that ADM blocked nuclear translocation of Trx induced by H/R. The results of the present study show that ADM regulates cellular ROS levels via the GSH and Trx system.
Kim
Su-Mi
SM
Department of Pathology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Kim
Jee-Youn
JY
Lee
Sun
S
Park
Jae-Hoon
JH
D053607:Adrenomedullin / Q000378:metabolism*; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D009336:Necrosis / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*
D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D053607:Adrenomedullin; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione