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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Wongrakpanich, Amaraporn; Morris, Angie S; Geary, Sean M; Joiner, Mei-Ling A; Salem, Aliasger K

Published In Int J Pharm, (2017 Mar 30)

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.

PubMed ID: 28167264 Exiting the NIEHS site

MeSH Terms: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors*; Cell Death/drug effects; Cells, Cultured; Isoproterenol/pharmacology; Lactic Acid/chemistry; Membrane Potential, Mitochondrial/drug effects; Mitochondria, Heart/drug effects*; Myocytes, Cardiac/cytology; Myocytes, Cardiac/drug effects*; Organophosphorus Compounds/chemistry*; Peptides/chemistry; Peptides/pharmacology*; Polyglycolic Acid/chemistry; Polylactic Acid-Polyglycolic Acid Copolymer; Protective Agents/chemistry; Protective Agents/pharmacology*; Rats; Reactive Oxygen Species/metabolism; Surface Properties

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