Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice.

IF 4 3区 医学 Q2 CELL BIOLOGY Disease Models & Mechanisms Pub Date : 2024-04-15 DOI:10.1242/dmm.050631
Katerina Mardilovich, Gregory Naylor, Linda Julian, Narisa Phinichkusolchit, Karen Keeshan, Karen Blyth, Michael F Olson
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Abstract

Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower in Eµ-Myc; Rock1 NC mice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death in Eµ-Myc; Rock1 NC mice bone marrows being more inflammatory. Rock1 WT recipient mice transplanted with pre-neoplastic Eµ-Myc; Rock1 NC bone marrow cells survived longer than mice transplanted with Eµ-Myc; Rock1 WT cells, indicating that the survival benefit was intrinsic to the Eµ-Myc; Rock1 NC bone marrow cells. The results suggest that the apoptotic death of Eµ-Myc; Rock1 NC cells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.
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抗Caspase的ROCK1表达可延长Eµ-Myc B细胞淋巴瘤小鼠的存活期。
细胞凋亡的特征是膜裂解和凋亡体形成。ROCK1 被 Caspase 酶裂解后会产生一个活性片段,在细胞凋亡过程中促进肌动蛋白介导的收缩和膜裂解。小鼠因表达 Eµ-Myc 转基因而迅速罹患 B 细胞淋巴瘤,表达抗 Caspase 的不可裂解 ROCK1(Rock1 NC)可延长小鼠的存活时间。与表达野生型 ROCK1(Rock1 WT)的 Eµ-Myc 小鼠相比,Eµ-Myc;Rock1 NC 小鼠的骨髓细胞数量明显减少,这与细胞周期轮廓的改变有关。Eµ-Myc;Rock1 NC小鼠的循环巨噬细胞数量较低,但骨髓巨噬细胞的水平较高,这与Eµ-Myc;Rock1 NC小鼠骨髓中自发的细胞死亡更具炎症性是一致的。与移植了 Eµ-Myc; Rock1 WT 细胞的小鼠相比,移植了肿瘤前 Eµ-Myc; Rock1 NC 骨髓细胞的 Rock1 WT 受体小鼠存活时间更长,这表明存活益处是 Eµ-Myc; Rock1 NC 骨髓细胞固有的。结果表明,Eµ-Myc; Rock1 NC细胞的凋亡在骨髓中产生了抑制增殖的微环境,从而减少了细胞数量,延长了B细胞淋巴瘤小鼠的存活时间。
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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