Host: The Japanese Pharmacological Society
Name : The 96th Annual Meeting of the Japanese Pharmacological Society
Number : 96
Location : [in Japanese]
Date : November 30, 2022 - December 03, 2022
Electrophiles have long been understood as bad guys that cause carcinogenesis and tissue damage. For example, acetaminophen undergoes metabolic activation, resulting in formation of highly reactive metabolites that covalently bind to cellular protein, thereby causing a toxic effect. This is a typical example of the recognized mechanism of toxicity seen in overdose of acetaminophen. Glutathione conjugation is known as a system for detoxifying electrophiles, but another strategy for inactivation of electrophiles was not understood. Furthermore, toxicology-oriented researchers were interested in the unfavorable intracellular events of exogenous electrophiles, and had no way of knowing the defense mechanism occurring outside the cell. In this lecture, I introduce 1) adaptive response through modulation of cellular redox signaling pathways (activation at low dose, disruption at high dose), 2) capture and inactivation through sulfur adduct formation by reactive sulfur molecules containing sulfane sulfur atoms, 3) trapping by cysteine excreted extracellularly during electrophilic stress.
