Antioxidative behavior of a2-macroglobulin in intervertebral disc degeneration.

IF 2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuhong Chen, Huaixiang Wei, Feng Xu
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引用次数: 0

Abstract

Background: To clarify if a2-macroglobulin (α2M) has an antioxidative effect during the progression of the intervertebral disc degeneration (IVDD).

Methods: The content of α2M and reactive oxygen species (ROS) were measured to compare mildly and severely degenerated human nucleus pulposus (NP) tissue by immunohistochemistry, mass spectrometry, and enzyme-linked immunosorbent assay (ELISA). Additionally, exogenic α2M was used to culture severely degenerated NP tissue in vitro. The effects of α2M on hypochlorite (HOCl)-treated NP cells were evaluated, containing antioxidative enzymes, ROS level, collagen II, and aggrecan expression, MMP3/13, and ADAMTS4/5.

Results: ROS level increased in severely degenerated NP, accompanying with a decreased α2M content. Supplement of α2M could decrease the ROS level of cultured NP in vitro, meanwhile, the MMP13 and ADAMTS4 expression were also reduced. It was found that treatment of HOCl resulted in oxidative damage to NP cells and decreased α2M expression in a dose and time-dependent manner. Furthermore, exogenic α2M stimulation reversed the HOCl-triggered ROS accumulation. The promotion of SOD1/2, CAT, GPX1, collagen II, and aggrecan, and suppression of MMP3/13, ADAMTS4/5 expression caused by α2M were also observed.

Conclusions: Our study indicates that α2M has an antioxidative ability in degenerated NP cells by promoting the antioxidative enzyme production.

Abstract Image

Abstract Image

Abstract Image

a2-巨球蛋白在椎间盘退变中的抗氧化行为。
背景:阐明a2-巨球蛋白(α2M)在椎间盘退变(IVDD)过程中是否具有抗氧化作用。方法:采用免疫组化、质谱、酶联免疫吸附法(ELISA)检测α2M和活性氧(ROS)含量,比较轻度和重度退行性人髓核(NP)组织。此外,外源α2M用于体外培养严重退化NP组织。研究α2M对次氯酸盐(HOCl)处理的NP细胞的影响,包括抗氧化酶、ROS水平、胶原II和聚集蛋白表达、MMP3/13和ADAMTS4/5。结果:严重退行性NP中ROS水平升高,α2M含量降低。补充α2M可降低体外培养NP的ROS水平,同时降低MMP13和ADAMTS4的表达。结果发现,HOCl处理可引起NP细胞氧化损伤,α2M表达呈剂量依赖性和时间依赖性。此外,外源α2M刺激逆转了hocl触发的ROS积累。α2M对SOD1/2、CAT、GPX1、collagen II、aggrecan的表达有促进作用,对MMP3/13、ADAMTS4/5的表达有抑制作用。结论:α2M通过促进抗氧化酶的产生,对变性NP细胞具有抗氧化作用。
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来源期刊
Journal of Medical Biochemistry
Journal of Medical Biochemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.00
自引率
12.00%
发文量
60
审稿时长
>12 weeks
期刊介绍: The JOURNAL OF MEDICAL BIOCHEMISTRY (J MED BIOCHEM) is the official journal of the Society of Medical Biochemists of Serbia with international peer-review. Papers are independently reviewed by at least two reviewers selected by the Editors as Blind Peer Reviews. The Journal of Medical Biochemistry is published quarterly. The Journal publishes original scientific and specialized articles on all aspects of clinical and medical biochemistry, molecular medicine, clinical hematology and coagulation, clinical immunology and autoimmunity, clinical microbiology, virology, clinical genomics and molecular biology, genetic epidemiology, drug measurement, evaluation of diagnostic markers, new reagents and laboratory equipment, reference materials and methods, reference values, laboratory organization, automation, quality control, clinical metrology, all related scientific disciplines where chemistry, biochemistry, molecular biology and immunochemistry deal with the study of normal and pathologic processes in human beings.
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