佩里抑制了C2毒素和Bordetella pertussis毒素中的C2毒素
Jinfang Jia1, Maria Braune-Yan1, Stefanie Lietz1
1Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center, 89081 Ulm, Germany.
Toxins
|July 28, 2023
概括
多佩里是一种Hsp70抑制剂,通过阻止细胞进入,保护细胞免受Bordetella pertussis毒素和Clostridium botulinum C2毒素的侵害. 这种重新利用提供了针对细菌毒素引起的疾病的潜在治疗策略.
科学领域:
- 微生物学 微生物学
- 毒理学 毒理学 毒理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 像Bordetella pertussis毒素 (PT) 和Clostridium botulinum C2毒素这样的细菌毒素利用宿主细胞的陪伴者进入.
- Hsp70是一个关键的伴侣,参与这些毒素的酶子单元转移到宿主细胞细胞质中.
- 抑制伴侣活性可以保护细胞免受毒素中介损伤.
研究的目的:
- 调查Hsp70抑制剂多佩里在保护细胞免受PT和C2毒素中毒方面的潜力.
- 为了确定多佩里是否影响毒素受体结合或酶活性.
主要方法:
- 通过分析特定基质的ADP-ribosylation来评估多佩里对毒素中毒的影响.
- 评估多佩里对C2毒素pH驱动的膜转位的影响.
- 在多佩里的存在下测量PT亚单元S1 (PTS1) 的细胞水平.
主要成果:
- 佩里抑制了PT和C2毒素的中毒.
- 佩里没有影响毒素的受体结合或酶活性.
- 多佩里抑制了C2毒素的膜转位,并降低了细胞内PTS1水平.
结论:
- 多佩里作为PT和C2毒素细胞吸收的强有力的抑制剂.
- 重新利用多佩里可能为由Hsp70依赖性细菌毒素引起的疾病提供治疗方法.
相关概念视频
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
705
Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...
The binding of dantrolene to the RYR1...
705
Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
398
Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
398
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
1.9K
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
1.9K
Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacological Actions
458
Nondepolarizing neuromuscular blockers prevent the membrane depolarization of muscle cells and inhibit muscle contraction. These are usually administered with anesthetics to achieve complete muscle relaxation. Upon administration, these drugs first block the small, rapidly contracting muscles of the face and hands, followed by the larger muscles of the trunk and the intercostal muscles. The diaphragm is the last muscle to be affected.
Although all competitive neuromuscular blockers are designed...
Although all competitive neuromuscular blockers are designed...
458
Depolarizing Blockers: Mechanism of Action
1.6K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
1.6K
Drugs for Treatment of Constipation-Predominant IBS
213
Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
213


