腺病毒介导的血氧酶-1基因表达刺激了血管光滑肌肉细胞中的亡
Xiao-ming Liu1, Gary B Chapman, Hong Wang
1Houston VA Medical Center and the Department of Medicine, Baylor College of Medicine, Houston, Tex 77030, USA.
Circulation
|January 5, 2002
概括
血管光滑肌细胞中的血氧酶-1 (HO-1) 过度表达会诱导亡,这表明血管疾病的基因疗法. 胆素和胆素也促进细胞死亡,但二氧化碳和铁却没有.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传输 细胞信号传输
- 基因治疗 基因治疗
背景情况:
- 血红氧酶-1 (HO-1) 在血管光滑肌细胞 (SMC) 中被诱导,但其具体作用尚不清楚.
- 在HO-1的代谢过程中,血红素被转化为白素,铁和一氧化碳 (CO).
研究的目的:
- 为了研究HO-1在老鼠大动脉SMC中的生物学作用.
- 为了确定HO-1过度表达对SMC增殖和亡的影响.
主要方法:
- 在使用重组腺病毒 (AdHO-1) 的老鼠大动脉SMC中过度表达HO-1.
- 评估HO-1表达,SMC扩散,细胞亡标志物 (DNA碎片,附件V,卡斯帕酶-3) 和p53水平.
- 将白素,白素,CO或铁给SMCs.
主要成果:
- AdHO-1感染增加了HO-1的表达,并以剂量依赖的方式抑制了SMC的扩散.
- 过度表达HO-1显著刺激了SMC亡,由增加的DNA碎片化,附件V标记,caspase-3激活和p53表达体现出来.
- 外源性 Biliverdin 和 bilirubin 促进了 SMC 亡,而 CO 和铁则没有.
结论:
- 过度表达HO-1,白或白会诱导血管光滑肌细胞的亡.
- 腺病毒介导的HO-1基因转移为封闭性血管疾病提供了潜在的治疗策略.
相关概念视频
Apoptosis
12.0K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
12.0K
Caspases
8.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
8.7K
The Extrinsic Apoptotic Pathway
6.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
The Intrinsic Apoptotic Pathway
6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
Regulation of Angiogenesis and Blood Supply
2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Cellular Injury V: Apoptosis and Autophagy
99
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
99


