TY - JOUR
T1 - Formation of cofilin-actin rods following cucurbitacin-B-induced actin aggregation depends on slingshot homolog 1-mediated cofilin hyperactivation
AU - Zhang, Yan Ting
AU - Ouyang, Dong Yun
AU - Xu, Li Hui
AU - Zha, Qing Bing
AU - He, Xian Hui
PY - 2013/10
Y1 - 2013/10
N2 - Accumulating evidence indicates that cucurbitacin B (CuB), as well as other cucurbitacins, damages the actin cytoskeleton in a variety of cell types. However, the underlying mechanism of such an effect is not well understood. In this study, we showed that CuB rapidly induced actin aggregation followed by actin rod formation in melanoma cells. Cofilin, a critical regulator of actin dynamics, was dramatically dephosphorylated (i.e., activated) upon CuB treatment. Notably, the activated cofilin subsequently formed rod-like aggregates, which were highly colocalized with actin rods, indicating the formation of cofilin-actin rods. Cofilin knockdown significantly suppressed rod formation but did not prevent actin aggregation. Furthermore, knockdown of the cofilin phosphatase Slingshot homolog 1 (SSH1), but not chronophin (CIN), alleviated CuB-induced cofilin hyperactivation and cofilin-actin rod formation. The activity of Rho kinase and LIM kinase, two upstream regulators of cofilin activation, was downregulated after cofilin hyperactivation. Pretreatment with a thiol-containing reactive oxygen species (ROS) scavenger N-acetyl cysteine, but not other ROS inhibitors without thiol groups, suppressed CuB-induced actin aggregation, cofilin hyperactivation and cofilin-actin rod formation, suggesting that thiol oxidation might be involved in these processes. Taken together, our results demonstrated that CuB-induced formation of cofilin-actin rods was mediated by SSH1-dependent but CIN-independent cofilin hyperactivation. J. Cell. Biochem. 114: 2415-2429, 2013. © 2013 Wiley Periodicals, Inc.
AB - Accumulating evidence indicates that cucurbitacin B (CuB), as well as other cucurbitacins, damages the actin cytoskeleton in a variety of cell types. However, the underlying mechanism of such an effect is not well understood. In this study, we showed that CuB rapidly induced actin aggregation followed by actin rod formation in melanoma cells. Cofilin, a critical regulator of actin dynamics, was dramatically dephosphorylated (i.e., activated) upon CuB treatment. Notably, the activated cofilin subsequently formed rod-like aggregates, which were highly colocalized with actin rods, indicating the formation of cofilin-actin rods. Cofilin knockdown significantly suppressed rod formation but did not prevent actin aggregation. Furthermore, knockdown of the cofilin phosphatase Slingshot homolog 1 (SSH1), but not chronophin (CIN), alleviated CuB-induced cofilin hyperactivation and cofilin-actin rod formation. The activity of Rho kinase and LIM kinase, two upstream regulators of cofilin activation, was downregulated after cofilin hyperactivation. Pretreatment with a thiol-containing reactive oxygen species (ROS) scavenger N-acetyl cysteine, but not other ROS inhibitors without thiol groups, suppressed CuB-induced actin aggregation, cofilin hyperactivation and cofilin-actin rod formation, suggesting that thiol oxidation might be involved in these processes. Taken together, our results demonstrated that CuB-induced formation of cofilin-actin rods was mediated by SSH1-dependent but CIN-independent cofilin hyperactivation. J. Cell. Biochem. 114: 2415-2429, 2013. © 2013 Wiley Periodicals, Inc.
KW - ACTIN AGGREGATION
KW - COFILIN
KW - COFILIN-ACTIN RODS
KW - CUCURBITACIN B
KW - MELANOMA
KW - SLINGSHOT HOMOLOG 1
UR - http://www.scopus.com/inward/record.url?scp=84882424327&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882424327&partnerID=8YFLogxK
U2 - 10.1002/jcb.24587
DO - 10.1002/jcb.24587
M3 - Article
C2 - 23695982
AN - SCOPUS:84882424327
SN - 0730-2312
VL - 114
SP - 2415
EP - 2429
JO - Journal of cellular biochemistry
JF - Journal of cellular biochemistry
IS - 10
ER -