药物诱导的氧化应激积极地阻止了卡斯巴酶激活和肝细胞亡
Rebekka Lambrecht1,2, Jasmin Jansen3,4, Franziska Rudolf1,5
1Biochemical Pharmacology, Department of Biology, University of Konstanz, Konstanz, Germany.
Cell death & disease
|September 8, 2024
概括
降醇 (乙氨基,APAP) 通过抑制卡斯帕斯,转移细胞亡到亡,导致细胞死亡. 这种开关是由氧化应激驱动的,可以用抗氧化剂逆转,突出了细胞氧化还原状态在细胞死亡决策中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
背景情况:
- 细胞死亡对健康和疾病至关重要,具有不同的模式.
- 了解细胞死亡信号通路对于破译细胞结果至关重要.
- 降醇 (乙氨基,APAP) 诱导的肝损伤包括没有卡斯巴酶激活的缩.
研究的目的:
- 研究由APAP引起的矛盾细胞死亡.
- 确定APAP抑制酶激活背后的机制.
- 阐明细胞氧化还原状态在APAP诱导的细胞死亡中的作用.
主要方法:
- 研究了APAP诱导的肝细胞死亡.
- 评估了酶激活和细胞形成.
- 测量了线粒体呼吸和细胞ATP水平.
- 研究了氧化应激和抗氧化剂的影响.
主要成果:
- APAP抑制了酶激活,促进了亡而不是亡.
- 观察到线粒体呼吸和ATP水平的降低,但并不是卡斯巴酶抑制的原因.
- 氧化应激被确定为APAP诱导的酶抑制的一个关键因素.
- 抗氧化剂的使用逆转了酶抑制和转向亡的过程.
结论:
- 细胞的氧化还原状态极大地影响了细胞亡和亡之间的决定.
- 由APAP诱导的细胞死亡表明,氧化应激直接影响caspase活动.
- 准细胞氧化还原平衡可能为APAP毒性提供治疗策略.
相关概念视频
The Intrinsic Apoptotic Pathway
6.4K
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...
6.4K
Peroxisomes
11.3K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
11.3K
Phase I Oxidative Reactions: Overview
247
Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
247
Electron Transport Chain: Complex I and II
12.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
12.2K
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
156
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
156
The Extrinsic Apoptotic Pathway
6.3K
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...
6.3K


