The chemical structure of 2,4-toluene diisocyanate conjugating with human serum albumin and it's cytotoxicity

• Main Author: 高意芸
• Other Authors: 劉佩珊
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/70242713140939751618

碩士 === 東吳大學 === 微生物學系 === 92 === Toluene diisocyanate (TDI) is a widely used as a chemical intermediate in the production of polyurethane products such as foams, coatings, and elastomers. In exposed workers, inhalation exposure TDI leads its binding with human serum albumin (HSA) and results significant decreases in lung function and asthma-like reaction. Firstly, investigated the conjugation of TDI-HSA and found the possible binding position of TDI was lysine on the 373 and 437 amino acid sequence of HSA. These binding sites are evidenced by the peptide fragments analysis by Maldi-TOF MS. In most affected workers, TDI-induced asthma is characterized by specific airway hyperresponsiveness to acetylcholine or methacholine. Therefore, we investigated the possible mechanisms involved in TDI-induced airway hyperresponsiveness to acetylcholine by observation [Ca2+]c changes under the stimulation of nicotinic and muscarinic acetylcholine receptors in the present or absent of TDI in human neuroblastoma cells. The results shows TDI can induce internal calcium release and capacitative calcium entry. Under the stimulation of nicotinic and muscarinic receptors, TDI suppressed their [Ca2+]c rise. We also found TDI was capable to inhibit P2X receptors, GABA receptors and voltage-sensitive calcium channels. However, the inhibition of TDI on muscarinic receptors was most dominant. We suggest that the suppression of TDI on muscarinic receptors was due to its capability releasing calcium from internal pools. In airways, TDI is possibly to act at the muscarinic receptors on the epithelial cells to suppress smooth muscle relaxation by shutting down the NO-signaling pathway that is initiated by the activation of muscarinic receptors on epithelial cells.