Int. J. Environ. Res. Public Health 2012, 9 490 regulates antioxidant response element (ARE)-mediated expression of -GCS heavy subunit and other xenobiotic metabolizing enzymes. Nrf2 binds to the cysteine-rich keap1 protein in the actin filaments as an inactive form in the cytoplasm. Upon oxidative stress such as As3+ exposure, modification of cysteine residues in the Keap1 protein results in the Nrf2 release and nuclear localization for ARE binding and transactivation of the genes [43]. Elevation of cellular metallothionein and -GCS/GSH may be a critical detoxification mechanism against As3+ toxicity. Tubulin heterodimer binds two GTP molecules, one exchangeable in -tubulin and another one nonexchangeale in -tubulin. Upon polymerization, GTP bound to  tubulin is hydrolyzed to GDP by intrinsic tubulin GTPase activity. The resulting GDP-tubulin exhibits a reduced affinity for its neighbors and undergoes disassembly [35]. Thus, MTs exhibit dynamic equilibrium, growing and shrinking by the addition or loss of tubulin dimers from the ends of protofilaments. As3+ has been reported to inactivate the GTP binding site on tubulins, thus inhibiting the MT assembly in vitro [44]. The hydrolysis of GTP to GDP in β-tubulin increases the curvature of protofilaments, destabilizing MTs [45]. This suggests that modulating the curvature status of MTs can change its stability. Taxol binding to the β-tubulin subunit, specifically to peptides 1–31, 217–231 and 297–293 [46], has been shown to straighten the GDP protofilament and slow down the transition of protofilaments from straight to a curved configuration [45]. Taxol stabilization of MTs has been reported to resist depolymerization by Ca2+, cold temperature, dilution, etc. [47]. Here, we go on to demonstrate taxol antagonism on disassembly of MTs by sulfhydryl-directed agents such as As3+ and NEM. Presumably, As3+ binding to tubulin -SH-groups may enhance the curvature of protofilaments, thus instabilizing MTs. In addition to the tubulin dimer, MTs also contain several minor proteins, i.e., MAPs. The procedures for metabolic labeling, extraction with detergent and Ca2+, analysis of MAPs and other related proteins on 2-D gels have been used in different cells in response to different agents [25,48]. As shown in our studies, As3+ induced disassembly of MTs. Autoradiograms of proteins present in the MT fraction under As3+ treatment conditions were compared with its “control” profile derived from cells without As3+ treatment to identify subtle changes in protein molecular species. A protein that is present in cells with intact MT but changed or absent when intact MT no longer exist in such cells (such as nocodazole and As3+ treatments) fulfilling the operational definition of MAPs. Because of its high resolution, the quantitative 2-D gel electrophoresis has been the most powerful technique used for identifying unknown MAP proteins. With this 2-D gel system, several MAP proteins have been identified [25,48]. However, only five of them were decreased by >50% in cells exposed to 10 μM As3+ [Figure 10(B)], indicating that not all MAPs were equally susceptible to this trivalent metalloid element. MAPs exist only in minute amounts in non-neuronal cells. Based on their apparent MW and pI on 2-D gels, none of these MAPs (Figure 10) appeared to resemble any existing MAP reported in the literature. This is not surprising since most MAPs identified so far, such as MAP1, MAP2, MAP3, Tau family and 210 kD protein (MAP4), etc., are from either the brain tissue or cells of neural origin [29,49-51]. Notably, several MAP, e.g., MAP-2 and Tau proteins isolated from the brain tissue, stimulate MT assembly and enhance MT stability both in vitro and in vivo [29,50]. Thus, results in giving for inhibition of MAPs by As3+ would lead to the enhancement of MT instability. Immunohistochemical studies indicated severe loss of tubulin synthesis and distribution in As3+-dosed lungs [Figure 4(A2)]. Since absorbed As3+ is distributed throughout the body [5,6], all types of lung cells are targets for As3+ insult including interstitial fibroblasts. In view of MT