对GS蛋白α子单元序列的反感性寡氧核酸加快了纤维细胞分化到脂肪细胞的过程
H Y Wang1, D C Watkins, C C Malbon
1Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Nature
|July 23, 1992
概括
霍乱毒素通过激活Gsαα,阻断3T3-L1纤维细胞分化成脂肪细胞. 针对Gs-alpha的反感性寡氧核酸加速了这种差异化,揭示了Gs-alpha独立于循环AMP的新角色.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 3T3-L1纤维细胞分化为脂肪细胞,积累脂质.
- G蛋白对于跨膜信号传递至关重要,并且可以自我调节.
- 在3T3-L1脂肪生成过程中,G蛋白水平发生显著变化.
研究的目的:
- 研究G蛋白,特别是Gsα在3T3-L1纤维细胞分化中的作用.
- 确定Gsα活性是否影响脂肪生成的速度和过程.
主要方法:
- 用霍乱毒素对3T3-L1细胞进行治疗,以激活Gs alpha.
- 使用针对Gs alpha的反感性寡氧核酸的药物.
- 监测脂质积累和分化的时间进程.
主要成果:
- 霍乱毒素抑制了脂肪细胞的分化.
- 反理性Gsα oligodeoxynucleotides显著加速了分化,将时间从7-10天缩短到大约3天.
- 百日咳毒素,福斯科林或迪布蒂瑞尔cAMP没有影响分化,这表明Gsα的作用独立于cAMP.
结论:
- Gsα活性在调节3T3-L1脂肪生成中发挥着关键的新型作用.
- 这种Gsα的调制是独立于细胞内循环AMP水平的变化.
相关概念视频
02:11Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Transcription is the synthesis of RNA molecules by RNA...
01:24Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
01:26Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
01:29Protein Folding Quality Check in the RER
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
01:23Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...