p38 MAPK in cardioprotection - are we there yet?
p38 MAPK in cardioprotection - are we there yet?
复制标题
DOI：
10.1111/bph.12901
复制
发表时间：
2015-04
影响因子：
7.3
通讯作者：
Marber MS
中科院分区：
文献类型：
--
作者：
Martin ED;Bassi R;Marber MS
PKS将磷酸从ATP转移到底物蛋白质的丝氨酸、苏氨酸或酪氨酸残基的侧链羟基上。这反过来可以改变蛋白质的功能，调节基本的细胞过程，包括新陈代谢、转录、生长、分裂、分化、运动和生存。PKs根据同源性被细分为多个家族。其中一类是应激激活的激酶，顾名思义，它是在细胞应激如毒素、细胞因子、机械变形和渗透应激时被激活的。成员包括p38MAPK家族，它由α，β，γ和δ组成，这两种亚型由不同的基因编码。这些激酶转导细胞外信号，协调适应和生存所需的细胞反应。然而，在心血管疾病和其他疾病状态下，这些相同的系统可能会触发适应不良反应，从而加剧而不是缓解疾病。这种情况类似于心力衰竭中的肾上腺素、血管紧张素和醛固酮信号，尽管这些激素对体内平衡很重要，但抑制是有益的。问题是，抑制p38是否会产生类似的好处？在这篇综述中，我们将讨论p38的结构和功能，p38抑制剂的历史及其在临床前研究中的应用。最后，我们将总结最近使用p38抑制剂进行的心血管临床试验的结果。
PKs transfer a phosphate from ATP to the side-chain hydroxyl group of a serine, threonine or tyrosine residue of a substrate protein. This in turn can alter that protein's function; modulating fundamental cellular processes including, metabolism, transcription, growth, division, differentiation, motility and survival. PKs are subdivided into families based on homology. One such group are the stress-activated kinases, which as the name suggests, are activated in response to cellular stresses such as toxins, cytokines, mechanical deformation and osmotic stress. Members include the p38 MAPK family, which is composed of α, β, γ and δ, isoforms which are encoded by separate genes. These kinases transduce extracellular signals and coordinate the cellular responses needed for adaptation and survival. However, in cardiovascular and other disease states, these same systems can trigger maladaptive responses that aggravate, rather than alleviate, the disease. This situation is analogous to adrenergic, angiotensin and aldosterone signalling in heart failure, where inhibition is beneficial despite the importance of these hormones to homeostasis. The question is whether similar benefits could accrue from p38 inhibition? In this review, we will discuss the structure and function of p38, the history of p38 inhibitors and their use in preclinical studies. Finally, we will summarize the results of recent cardiovascular clinical trials with p38 inhibitors.
登录
查看更多内容
影响因子：
16.8
作者：
De Nicola, Gian Felice;Martin, Eva Denise;Chaikuad, Apirat;Bassi, Rekha;Clark, James;Martino, Luigi;Verma, Sharwari;Sicard, Pierre;Tata, Renee;Atkinson, R. Andrew;Knapp, Stefan;Conte, Maria R.;Marber, Michael S.
通讯作者：
Marber, Michael S.
影响因子：
24
作者：
Bellahcene, Mohamed;Jacquet, Sebastien;Marber, Michael S.
通讯作者：
Marber, Michael S.
影响因子：
7.3
作者：
Alexander SP;Benson HE;Faccenda E;Pawson AJ;Sharman JL;Spedding M;Peters JA;Harmar AJ;CGTP Collaborators
通讯作者：
CGTP Collaborators
影响因子：
4.8
作者：
Bell, M;Capone, R;Engelberg, D
通讯作者：
Engelberg, D
影响因子：
15.9
作者：
Braz, JC;Bueno, OF;Molkentin, JD
通讯作者：
Molkentin, JD