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Expression of αB-crystallin overrides the anti-apoptotic activity of XIAP

机译：αB-晶状体蛋白的表达超过了XIAP的抗凋亡活性

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摘要

Although crystallins are major structural proteins in the lens, α-crystallins perform non-lens functions, and αB-crystallin has been shown to act as an anti-apoptotic mediator in various cells. The present study was undertaken to examine whether αB-crystallin expressed in human malignant glioma cells exerts anti-apoptotic aci-tivity. In addition, we sought to elucidate the mechanism underlying any observed anti-apoptotic function of αB-crystallin in these cells. Three glioma cell lines, U373MG, U118MG, and T98G, were used. We observed that only the U373MG cell line expresses αB- crystallin, whereas the other 2 glioma cell lines, U118MG and T98G, demonstrated no endogenous expression of αB-crystallin. We next observed that the silencing of αB-crystallin sensitized U373MG cells to suberoylanilide hydroxamic acid (SAHA)-induced apo-ptosis and that αB-crystallin associates with caspase-3 and XIAP. Because XIAP is the most potent suppressor of mammalian apoptosis through the direct binding with caspases, we assessed whether XIAP also plays an anti-apoptotic role in SAHA-induced apoptosis in αB-crystallin-expressing U373MG cells. Of note, the silencing of XIAP did not alter the amount of cell death induced by SAHA, indicating that XIAP does not exert an anti-apoptotic activity in U373MG cells. We then determined whether the ectopic expression of αB-crystallin in glioma cells caused a loss of the anti-apoptotic activity of XIAP. Accordingly, we established 2 αB-crystallin over-expressing glioma cell lines, U118MG and T98G, and found that the silencing of XIAP did not sensitize these cells to SAHA-induced apoptosis. These findings suggest that aB-crystallin expressed in glioma cells overrides the anti-apoptotic activity exerted by XIAP.
机译：尽管晶状体蛋白是晶状体中的主要结构蛋白，但α-晶状体蛋白具有非晶状体功能，并且已证明αB-晶状体蛋白在各种细胞中起抗凋亡介质的作用。进行本研究以检查在人类恶性神经胶质瘤细胞中表达的αB-晶状体蛋白是否具有抗凋亡活性。此外，我们试图阐明在这些细胞中观察到的任何αB-晶状体抗凋亡功能的潜在机制。使用了三种神经胶质瘤细胞系U373MG，U118MG和T98G。我们观察到只有U373MG细胞系表达αB-晶状体蛋白，而其他2个神经胶质瘤细胞系U118MG和T98G则没有内源性表达αB-晶状体蛋白。接下来，我们观察到沉默的αB-晶状体蛋白可使U373MG细胞对亚油酰苯胺异羟肟酸（SAHA）诱导的垂体细胞凋亡，并且αB-晶状体蛋白与caspase-3和XIAP相关。由于XIAP通过与胱天蛋白酶直接结合，是最有效的哺乳动物细胞凋亡抑制剂，因此我们评估了XIAP是否在SAHA诱导的表达αB-晶状蛋白的U373MG细胞凋亡中也发挥抗凋亡作用。值得注意的是，XIAP沉默并没有改变SAHA诱导的细胞死亡数量，这表明XIAP在U373MG细胞中不发挥抗凋亡活性。然后，我们确定神经胶质瘤细胞中异位表达αB-晶状体蛋白是否引起XIAP的抗凋亡活性丧失。因此，我们建立了2个过表达αB-crystallin的神经胶质瘤细胞系U118MG和T98G，发现XIAP的沉默不会使这些细胞对SAHA诱导的细胞凋亡敏感。这些发现表明，在神经胶质瘤细胞中表达的aB-晶状体蛋白优于XIAP发挥的抗凋亡活性。

著录项

  • 来源
    《Neuro-Oncology》 |2012年第11期|1332-1345|共14页
  • 作者

    Jee Suk Lee; Hye Young Kim; Na Young Jeong; Sang Yeob Lee; Young Geol Yoon; Yung Hyun Choi; Chunlan Yan; In-Sun Chu; Hyungjong Koh; Hwan Tae Park; Young Hyun Yoo;

  • 作者单位

    Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, Republic of Korea;

    Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, Republic of Korea;

    Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, Republic of Korea;

    Department of Rheumatology, College of Medicine, Dong-A University, Busan, Republic of Korea;

    Present Address: Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 367-805, South Korea;

    Department of Biochemistry and Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine, Busan, Republic of Korea;

    Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China;

    Korean Bioinformation Center, KRIBB, Daejeon, Republic of Korea;

    Department of Pharmacology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, Republic of Korea;

    Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University, Busan, South Korea;

    Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, 3-1 Dongdaesin-dong, Seo-gu, Busan 602-714, Republic of Korea;

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  • 正文语种 eng
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  • 关键词

    αB-crystallin; apoptosis; glioma; SAHA; XIAP;

    机译：αB-晶状蛋白细胞凋亡胶质瘤SAHA;夏普;

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