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Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury.


ABSTRACT: 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 was taken up by mitochondria and successfully reduced reactive oxygen species (ROS) caused by Isoprenaline (ISO) in a differentiated rat cardiomyocyte-like cell line. When cells were treated with TPP-CIP prior to 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 has the potential to be used in protection against ischemia/reperfusion injury.

SUBMITTER: Wongrakpanich A 

PROVIDER: S-EPMC5401631 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury.

Wongrakpanich Amaraporn A   Morris Angie S AS   Geary Sean M SM   Joiner Mei-Ling A MA   Salem Aliasger K AK  

International journal of pharmaceutics 20170203 1-2


An excess of calcium (Ca<sup>2+</sup>) influx into mitochondria during mitochondrial re-energization is one of the causes of myocardial cell death during ischemic/reperfusion injury. This overload of Ca<sup>2+</sup> triggers the mitochondrial permeability transition pore (mPTP) opening which leads to programmed cell death. During the ischemic/reperfusion stage, the activated Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) enzyme is responsible for Ca<sup>2+</sup> influx. To reduc  ...[more]

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