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在佛波酯(PMA)刺激THP - 1细胞分化为巨噬细胞的过程中,RhoGDIβ在天冬氨酸19位点发生不依赖凋亡的裂解。

Apoptosis‑independent cleavage of RhoGDIβ at Asp19 during PMA‑stimulated differentiation of THP‑1 cells to macrophages.

作者信息

Ota Takahide, Jiang Yong-Sheng, Fujiwara Mamoru, Tatsuka Masaaki

机构信息

Division of Tumor Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920‑02, Japan.

Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

出版信息

Mol Med Rep. 2017 Apr;15(4):1722-1726. doi: 10.3892/mmr.2017.6199. Epub 2017 Feb 13.

Abstract

Rho GDP-dissociation inhibitor β (RhoGDIβ), a regulator of the Rho family of proteins, is expressed abundantly in the hematopoietic cell lineage. During apoptosis of hematopoietic cells, RhoGDIβ is cleaved by caspase‑3 at Asp19 and this cleaved form (Δ19‑RhoGDIβ) has been implicated in the apoptotic pathway. To clarify the role of RhoGDIβ in hematopoietic cells, the present study performed immunoblotting and immunofluorescence staining to examine the expression of RhoGDIβ and ∆19‑RhoGDIβ during phorbol 12‑myristate 13‑acetate (PMA)‑stimulated differentiation of human THP‑1 monocytic cells to macrophages. During differentiation of the THP‑1 cells to macrophages, the expression of RhoGDIβ remained stable; however, the expression of Δ19‑RhoGDIβ increased, particularly in well‑spreading, non‑apoptotic cells, which differentiated into macrophages. These results suggested that Δ19‑RhoGDIβ has an apoptosis‑independent role in the PMA‑induced differentiation of THP‑1 cells to macrophages.

摘要

Rho GDP解离抑制剂β(RhoGDIβ)是Rho蛋白家族的一种调节因子,在造血细胞谱系中大量表达。在造血细胞凋亡过程中,RhoGDIβ在天冬氨酸19位被半胱天冬酶-3切割,这种切割形式(Δ19-RhoGDIβ)与凋亡途径有关。为了阐明RhoGDIβ在造血细胞中的作用,本研究进行了免疫印迹和免疫荧光染色,以检测佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)刺激人THP-1单核细胞向巨噬细胞分化过程中RhoGDIβ和Δ19-RhoGDIβ的表达。在THP-1细胞向巨噬细胞分化过程中,RhoGDIβ的表达保持稳定;然而,Δ19-RhoGDIβ的表达增加,特别是在分化为巨噬细胞的铺展良好、非凋亡细胞中。这些结果表明,Δ19-RhoGDIβ在PMA诱导的THP-1细胞向巨噬细胞分化中具有不依赖凋亡的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef2e/5365007/3f32770e8272/MMR-15-04-1722-g00.jpg

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