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蛋白酶抑制剂和酰化刺激蛋白在3T3-L1细胞脂肪生成中的作用。

Role of protease inhibitors and acylation stimulating protein in the adipogenesis in 3T3-L1 cells.

作者信息

Soliman Mohamed Mohamed, El-Senosi Yakut Abdel-Fattah, Salem Maysara Mahmoud, Abdel Hamid Omniya Mahmoud, Kazuhiro Kimura

机构信息

Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, 020-013, Egypt.

出版信息

J Vet Sci. 2009 Sep;10(3):197-201. doi: 10.4142/jvs.2009.10.3.197.

DOI:10.4142/jvs.2009.10.3.197
PMID:19687619
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2801122/
Abstract

Treatment of AIDS (HIV) and hepatitis C virus needs protease inhibitors (PI) to prevent viral replication. Uses of PI in therapy are usually associated with a decrease in body weight and dyslipidemia. Acylation stimulating protein (ASP) is a protein synthesized in adipocytes to increase triglycerides biosynthesis, for that the relation of PI and ASP to adipogenesis is tested in this work. ASP expression was increased during 3T3-L1 differentiation and reached a peak at day 8 with cell maturation. Addition of PI during adipocytes differentiation dose dependently and significantly (p < 0.5) inhibited the degree of triglycerides (TG) accumulation. Moreover, presence of ASP (450 ng/mL) in media significantly (p < 0.5) stimulated the degree of TG accumulation and there was additive stimulation for ASP when added with insulin (10 microg/mL). Finally, when ASP in different doses (Low, 16.7; Medium, 45 and High, 450 ng/mL) incubated with a dose of x150 PI, ASP partially inhibited the PI-inhibited adipogenesis and TG accumulation. The results in this study show that PI inhibit lipids accumulation and confirm role of ASP in TG biosynthesis and adipogenesis.

摘要

艾滋病(HIV)和丙型肝炎病毒的治疗需要蛋白酶抑制剂(PI)来阻止病毒复制。PI在治疗中的使用通常与体重减轻和血脂异常有关。酰化刺激蛋白(ASP)是一种在脂肪细胞中合成的蛋白质,用于增加甘油三酯的生物合成,因此在本研究中测试了PI和ASP与脂肪生成的关系。在3T3-L1分化过程中,ASP表达增加,并在第8天随着细胞成熟达到峰值。在脂肪细胞分化过程中添加PI呈剂量依赖性,且显著(p < 0.5)抑制甘油三酯(TG)的积累程度。此外,培养基中存在ASP(450 ng/mL)显著(p < 0.5)刺激了TG的积累程度,并且当与胰岛素(10 μg/mL)一起添加时,对ASP有累加刺激作用。最后,当不同剂量(低剂量,16.7;中剂量,45;高剂量,450 ng/mL)的ASP与150倍剂量的PI一起孵育时,ASP部分抑制了PI抑制的脂肪生成和TG积累。本研究结果表明,PI抑制脂质积累,并证实了ASP在TG生物合成和脂肪生成中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/4ef8b214d385/jvs-10-197-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/bb28605c5955/jvs-10-197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/138587ff1f96/jvs-10-197-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/278aae1797b7/jvs-10-197-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/16209e45c587/jvs-10-197-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/4ef8b214d385/jvs-10-197-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/bb28605c5955/jvs-10-197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/138587ff1f96/jvs-10-197-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/278aae1797b7/jvs-10-197-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/16209e45c587/jvs-10-197-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93f3/2801122/4ef8b214d385/jvs-10-197-g005.jpg

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Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors or specific inhibitor lactacystin leads to a defect in adipogenesis, which involves matrix metalloproteinase-9.HIV蛋白酶抑制剂或特异性抑制剂乳胞素对人前脂肪细胞蛋白酶体活性的抑制会导致脂肪生成缺陷,这一过程涉及基质金属蛋白酶-9。
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Acylation-stimulating protein (ASP)/complement C3adesArg deficiency results in increased energy expenditure in mice.酰化刺激蛋白(ASP)/补体C3adesArg缺乏导致小鼠能量消耗增加。
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