Study of the molecular mechanisms of carbon monoxide on the induction of cyclooxygenase-2 in macrophage and microglia

• Main Authors: Pei-Yi Wu, 吳珮儀
• Other Authors: Yu-Chih Liang
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/70954108486727249271

碩士 === 臺北醫學大學 === 醫學技術學系 === 95 === The enzyme heme oxygenase (HO) degrades heme to produce biliverdin/bilirubin, ferrous iron and carbon monoxide (CO). Many biological functions of HO have been attributed to its enzymatic byproduct carbon monoxide (CO) that exhibits anti-oxidative, vasodilation, and neurotransmission activities in the central or peripheral nervous system, as well as anti-inflammatory, anti-apoptotic, or anti-proliferative potential in many cells. Carbon monoxide-releasing molecules (CO-RMs) are emerging as a new class of pharmacological agents that regulates important cellular function by liberating CO in biological system. In this study, we used both CO-RMs and CO gas to examine the regulation of cyclooxygenase-2 (COX-2) expression in microglia/macrophage. Western blot and RT-PCR analysis demonstrated that CO-RMs and CO gas (500 ppm) significantly inhibited the protein and mRNA expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated (BV2 and EOC13.31) microglia and (RAW264.7) macrophage. However, CO-RMs and CO gas up-regulated COX-2 expression in the cells with or without LPS. CO-RMs time-dependently induced the phosphorylation of MAPKs and Akt. In addition, the induction of COX-2 could be reversed by PKG, p38, Erk and JNK inhibitors. The results suggest that the induction of COX-2 expression by CO might mediate PKG, p38, Erk and JNK. Further works are to investigate whether induction of COX-2 contribute to the neuron death in primary cortical cells exposed to CO.