Dynamics of gamma-tubulin cytoskeleton in HL-60 leukemia cells undergoing differentiation and apoptosis by all-trans retinoic acid

作者：Shariftabrizi Ahmad; Ahmadian Shahin^*; Pazhang Yaghub

来源：Molecular Medicine Reports, 2012, 5(2): 545-551.

DOI：10.3892/mmr.2011.635

• apoptosis
• differentiation
• gamma-tubulin
• HL-60 cells
• microtubules

Microtubules are important components of the cell cytoskeleton, participating in protein localization and cell signaling. The capacity of leukemia cells to re-organize their microtubules is considered an integral part of differentiation in these cells in order to become mature granulocytes through treatment with all-trans retinoic acid (ATRA), an established drug for treating acute promyelocytic leukemia. In this study we examined gamma-, alpha- and acetylated-alpha-tubulin content, their patterns of distribution in the cytoplasm, and the potency of centrosomes in re-organizing microtubules in different stages of ATRA-induced differentiation and apoptosis of the HL-60 cell line. The gamma-tubulin content was dramatically increased following differentiation of HL-60 cells, and was then decreased after apoptosis. We also found that gamma-tubulin had a diffuse, cytoplasmic pattern following apoptosis compared to the focal, centrosomal accumulation of gamma-tubulin in differentiated cells. Differentiated cells had the ability to re-organize their microtubule network following nocodazole challenge testing, whereas undifferentiated cells did not show a similar ability. alpha-tubulin was more regularly organized in differentiated cells, and did not reveal any specific pattern of polymerization in apoptotic cells. Acetylated-alpha-tubulin generally followed the same organization patterns after differentiation, as that which occurred for a-tubulin. Our data is suggestive of a centrosomal and organized nucleation pattern of microtubules in HL-60 cells following differentiation, possibly mediated through up-regulation of gamma-tubulin.

• 出版日期2012-2