Identifying the Mouse Lung Citrullinome Following Acute Asbestos Exposure

Faculty Mentor Information

Dr. Kinta Serve (Mentor), Idaho State University

Abstract

Asbestos exposure increases the risk of many pulmonary diseases and has been linked to autoimmune responses. These autoimmune responses may be in part due to citrullination of plasminogen and other lung proteins. Citrullination is the post-translational modification of arginine residues in target proteins to citrulline, which is catalyzed by peptidylarginine deiminase enzymes (PADS). This can affect the conformation, function, and half-life of the protein. While PADs are commonly expressed in specific areas throughout the body, an increased expression has been seen in lung tissue following asbestos exposure. Citrullination has potential links to tumorigenesis and autoimmunity, with antibodies forming against citrullinated proteins. After low-dose asbestos exposure, we have seen increased PAD expression in the pleural cavity and lung tissue through immunohistochemistry stain and western blot. These increases in PADs have caused larger numbers of citrullinated proteins within the lung tissue, which was verified by fluorescent stain. The expression is highest at 7 days following exposure and decreases over time, indicating that the PAD expression is an acute response to asbestos. At 21 days post-exposure we see increased citrullination in the lung tissue.

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Identifying the Mouse Lung Citrullinome Following Acute Asbestos Exposure

Asbestos exposure increases the risk of many pulmonary diseases and has been linked to autoimmune responses. These autoimmune responses may be in part due to citrullination of plasminogen and other lung proteins. Citrullination is the post-translational modification of arginine residues in target proteins to citrulline, which is catalyzed by peptidylarginine deiminase enzymes (PADS). This can affect the conformation, function, and half-life of the protein. While PADs are commonly expressed in specific areas throughout the body, an increased expression has been seen in lung tissue following asbestos exposure. Citrullination has potential links to tumorigenesis and autoimmunity, with antibodies forming against citrullinated proteins. After low-dose asbestos exposure, we have seen increased PAD expression in the pleural cavity and lung tissue through immunohistochemistry stain and western blot. These increases in PADs have caused larger numbers of citrullinated proteins within the lung tissue, which was verified by fluorescent stain. The expression is highest at 7 days following exposure and decreases over time, indicating that the PAD expression is an acute response to asbestos. At 21 days post-exposure we see increased citrullination in the lung tissue.