Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk.
Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk.
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通过激酶-激酶串扰导致的应激驱动的心脏钙处理不当。
DOI：
10.1007/s00424-021-02533-2
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Ai X
中科院分区：
文献类型：
--
作者：
McKee C;Bare DJ;Ai X
心肌细胞中钙稳态对正常心脏功能的调节至关重要。异常的钙动力学，如改变摄取的肌浆网（SR）Ca 2 +-ATP酶和增加舒张SR钙漏参与发展适应不良的心脏重塑在病理条件下。Ca 2 +/钙调素依赖性蛋白激酶II-δ（CaMKIIδ）是心肌细胞钙调节异常的关键分子。升高的细胞应激被认为是病理性重塑过程中的共同特征，c-jun N-末端激酶（JNK）是一种重要的应激激酶，其响应于内在和外在应激刺激而被激活。我们的实验室最近确定了JNK亚型2（JNK 2）在应激心脏中CaMKIIδ表达、激活和CaMKIIδ依赖性SR Ca 2+处理不当中的特异性作用。本文综述了目前对生理和病理条件下心脏SR钙处理的理解，以及新近发现的CaMKIIδ依赖性SR Ca 2+异常处理中应激激酶JNK 2的贡献。本文还对JNK 2在CaMKIIδ表达和激活中的双重作用进行了讨论。
Calcium homeostasis in the cardiomyocyte is critical to the regulation of normal cardiac function. Abnormal calcium dynamics such as altered uptake by the sarcoplasmic reticulum (SR) Ca2+-ATPase and increased diastolic SR calcium leak are involved in the development of maladaptive cardiac remodeling under pathological conditions. Ca2+/calmodulin-dependent protein kinase II-δ (CaMKIIδ) is a well-recognized key molecule in calcium dysregulation in cardiomyocytes. Elevated cellular stress is known as a common feature during pathological remodeling, and c-jun N-terminal kinase (JNK) is an important stress kinase that is activated in response to intrinsic and extrinsic stress stimuli. Our lab recently identified specific actions of JNK isoform 2 (JNK2) in CaMKIIδ expression, activation, and CaMKIIδ-dependent SR Ca2+ mishandling in the stressed heart. This review focuses on the current understanding of cardiac SR calcium handling under physiological and pathological conditions as well as the newly identified contribution of the stress kinase JNK2 in CaMKIIδ-dependent SR Ca2+ abnormal mishandling. The new findings identifying dual roles of JNK2 in CaMKIIδ expression and activation are also discussed in this review.