Cytotoxic effects of dynorphins through nonopioid intracellular mechanisms.
Cytotoxic effects of dynorphins through nonopioid intracellular mechanisms.
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强啡肽通过非阿片类细胞内机制的细胞毒性作用。
DOI：
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发表时间：
2001
影响因子：
3.7
通讯作者：
Georgy Bakalkin
中科院分区：
文献类型：
--
作者：
K. Tan;G. Cebers;T. Yakovleva;Bee Hoon Goh;I. Gileva;K. Reznikov;M. Aguilar;K. Hauser;L. Terenius;Georgy Bakalkin
强啡肽A是一种强啡肽原衍生肽，能够诱导神经功能障碍和神经元死亡。为了研究强啡肽的体外细胞毒性，将强啡肽原衍生的肽加入非神经元和神经元细胞的培养基中或通过脂质转染或电穿孔递送到这些细胞中。当向培养基中加入肽时，细胞不受细胞外暴露的影响。相反，当强啡肽A或由强啡肽A和B组成的“大强啡肽”转染到细胞中时，活细胞的数量显著减少。大强啡肽比强啡肽A更有效，而强啡肽B、强啡肽B-29、[Arg（11，13）]-强啡肽A（-13）-Gly-NH-（CH（2））（5）-NH（2）（一种选择性κ-阿片受体激动剂）和聚-L-赖氨酸（一种比大强啡肽带更多正电荷的碱性肽）对细胞活力没有影响。阿片受体拮抗剂纳洛酮不能阻止强啡肽的细胞毒性。因此，毒性作用具有结构选择性，但不通过阿片受体介导。当大的强啡肽通过脂质体转染进入细胞时，它主要定位在细胞质中而不是细胞核中。大强啡肽似乎通过凋亡机制诱导毒性，该机制可能涉及与p53肿瘤抑制蛋白的协同相互作用。有人提出，大强啡肽诱导细胞死亡凭借其净正电荷和集群的碱性氨基酸，模仿（从而可能干扰）参与蛋白质-蛋白质相互作用的基本结构域。这些作用可能与强啡肽在脑和脊髓中的病理生理作用以及控制高水平表达强啡肽原的肿瘤细胞死亡有关。
Dynorphin A, a prodynorphin-derived peptide, is able to induce neurological dysfunction and neuronal death. To study dynorphin cytotoxicity in vitro, prodynorphin-derived peptides were added into the culture medium of nonneuronal and neuronal cells or delivered into these cells by lipofection or electroporation. Cells were unaffected by extracellular exposure when peptides were added to the medium. In contrast, the number of viable cells was significantly reduced when dynorphin A or "big dynorphin," consisting of dynorphins A and B, was transfected into cells. Big dynorphin was more potent than dynorphin A, whereas dynorphin B; dynorphin B-29; [Arg(11,13)]-dynorphin A(-13)-Gly-NH-(CH(2))(5)-NH(2), a selective kappa-opioid receptor agonist; and poly-l-lysine, a basic peptide more positively charged than big dynorphin, failed to affect cell viability. The opioid antagonist naloxone did not prevent big dynorphin cytotoxicity. Thus, the toxic effects were structure selective but not mediated through opioid receptors. When big dynorphin was delivered into cells by lipofection, it became localized predominantly in the cytoplasm and not in the nuclei. Big dynorphin appeared to induce toxicity through an apoptotic mechanism that may involve synergistic interactions with the p53 tumor-suppressor protein. It is proposed that big dynorphin induces cell death by virtue of its net positive charge and clusters of basic amino acids that mimic (and thereby perhaps interfere with) basic domains involved in protein-protein interactions. These effects may be relevant for a pathophysiological role of dynorphins in the brain and spinal cord and for control of death of tumor cells, which express prodynorphin at high levels.
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影响因子：
16.2
作者：
CORY, AH;OWEN, TC;CORY, JG
通讯作者：
CORY, JG
DOI：
--
发表时间：
1999-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
A. Remmers;M. Clark;A. Mansour;H. Akil;J. Woods;F. Medzihradsky
通讯作者：
A. Remmers;M. Clark;A. Mansour;H. Akil;J. Woods;F. Medzihradsky
(去酪氨酰)强啡肽 A(2-17) 与 NMDA 受体的高亲和力相互作用。
DOI：
--
发表时间：
1999
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Tang,Q;Gandhoke,R;Burritt,A;Hruby,VJ;Porreca,F;Lai,J
通讯作者：
Lai,J
3H-纳洛酮苯甲酰腙在 MOR-1 转染的中国仓鼠卵巢细胞中的结合：G 蛋白依赖性拮抗剂结合的证据。
DOI：
--
发表时间：
1998
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Brown,GP;Pasternak,GW
通讯作者：
Pasternak,GW
溶液中强啡肽-(1-13) 和 β-内啡肽与硫酸脑苷脂竞争性结合。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Wu,CS;Lee,NM;Loh,HH;Yang,JT
通讯作者：
Yang,JT