Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury.
Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury.
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DOI：
10.1016/j.ijpharm.2017.01.061
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发表时间：
2017-03-30
影响因子：
5.8
通讯作者：
Salem AK
中科院分区：
文献类型：
--
作者：
Wongrakpanich A;Morris AS;Geary SM;Joiner MA;Salem AK
An excess of calcium (Ca2+) influx into mitochondria during mitochondrial re-energization is one of the causes of myocardial cell death during ischemic/reperfusion injury. This overload of Ca2+ triggers the mitochondrial permeability transition pore (mPTP) opening which leads to programmed cell death. During the ischemic/reperfusion stage, the activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) enzyme is responsible for Ca2+ influx. To reduce CaMKII-related cell death, sub-micron particles composed of poly(lactic-co-glycolic acid) (PLGA), loaded with a CaMKII inhibitor peptide were fabricated. The CaMKII inhibitor peptide-loaded (CIP) particles were coated with a mitochondria targeting moiety, triphenylphosphonium cation (TPP), which allowed the particles to accumulate and release the peptide inside mitochondria to inhibit CaMKII activity. The fluorescently labeled TPP-CIP were taken up by mitochondria and successfully reduced ROS caused by Isoprenaline (ISO) in a differentiated rat cardiomyocyte-like cell line. When cells were treated with TPP-CIP prior ISO exposure, they maintained mitochondrial membrane potential. The TPP-CIP protected cells from ISO-induced ROS production and decreased mitochondrial membrane potential. Thus, TPP-CIP have the potential to be used in protection against ischemia/reperfusion injury.
