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

Autor: Aliasger K. Salem, Angie S. Morris, Sean M. Geary, Mei-ling A. Joiner, Amaraporn Wongrakpanich
Rok vydání: 2016
Předmět:
0301 basic medicine
Programmed cell death
Surface Properties
Pharmaceutical Science
chemistry.chemical_element
02 engineering and technology
Mitochondrion
Calcium
Protective Agents
Mitochondria
Heart
Article
03 medical and health sciences
Organophosphorus Compounds
Polylactic Acid-Polyglycolic Acid Copolymer
Ca2+/calmodulin-dependent protein kinase
medicine
Animals
Myocytes
Cardiac
Lactic Acid
Cells
Cultured
Membrane potential
chemistry.chemical_classification
Membrane Potential
Mitochondrial
Reactive oxygen species
Cell Death
Isoproterenol
021001 nanoscience & nanotechnology
medicine.disease
Cell biology
Rats
030104 developmental biology
Biochemistry
chemistry
Mitochondrial permeability transition pore
0210 nano-technology
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Peptides
Reactive Oxygen Species
Reperfusion injury
Polyglycolic Acid
Zdroj: International journal of pharmaceutics. 520(1-2)
ISSN: 1873-3476
Popis: 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.
Databáze: OpenAIRE
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