The signal transduction pathway for arsenite-induced cofilin activation

• Main Authors: Ni, Wan Ching, 倪婉晴
• Other Authors: Lin, Lih Yuan
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/01658975697214232694

碩士 === 國立清華大學 === 分子與細胞生物研究所 === 103 === Cadmium, arsenic, lead, and mercury are non-essential elements for plant or animal life. Excessive uptake may cause severe toxicological effect to organisms. Previous studies indicated that cadmium affects the polymerization of actin cytoskeleton. And the polymerization of actin filament is regulated by cofilin activity. Previous study from our laboratory indicated that cadmium treatment activates cofilin activity via PI3K/Rac1/PKD1/SSH1L cascade. We investigated in this study the effects of arsenite, lead, and mercury on cofilin activity and the involved signaling pathway in HEK293 cells. We found that the treatment of arsenite increased cofilin activity and decreased PTEN protein level. However, overexpression of PTEN did not affect arsenite-induced cofilin activation. PTEN is a negative regulator of PI3K pathway. Addition of PI3K inhibitor had also no effect on cofilin activity. Further study of downstream effectors indicated that Rac1, RhoA, and PKD1 was not involved in the activation pathway. Reportedly, cofilin activity modulates by ROCK through Ras/Raf/MEK/p21 pathway. We found that ERK would be activated in the treatment of arsenite. However, addition of MEK inhibitor did not affect arsenite-induced cofilin activity. We also found that p21 protein level in cells was not altered by arsenite but mRNA level of ROCK was decrease. On the other hand, cofilin activity is modulated mainly by LIMK and SSH1. We found that arsenite treatment increased SSH1L activity but decreased LIMK1 protein level. Our results indicated that ROCK/LIMK and SSH1L coordinately regulate arsenite-induced cofilin activation.