title: Examining efficacy of "TAT-less" delivery of a peptide against the L-type calcium channel in cardiac ischemia-reperfusion injury.
abstract: Increased calcium influx through the L-type Ca(2+) channel or overexpression of the alpha subunit of the channel induces cardiac hypertrophy. Cardiac hypertrophy results from increased oxidative stress and alterations in cell calcium levels following ischemia-reperfusion injury and is an independent risk factor for increased morbidity and mortality. We find that decreasing the movement of the auxiliary beta subunit with a peptide derived against the alpha-interacting domain (AID) of the channel attenuates ischemia-reperfusion injury. We compared the efficacy of delivering the AID peptide using a trans-activator of transcription (TAT) sequence with that of the peptide complexed to multifunctional polymeric nanoparticles. The AID-tethered nanoparticles perfused through the myocardium more diffusely and associated with cardiac myocytes more rapidly than the TAT-labeled peptide but had similar effects on intracellular calcium levels. The AID-complexed nanoparticles resulted in a similar reduction in release of creatine kinase and lactate dehydrogenase after ischemia-reperfusion to the TAT-labeled peptide. Since nanoparticle delivery also holds the potential for dual drug delivery, we conclude that AID-complexed nanoparticles may provide an effective platform for peptide delivery in cardiac ischemia-reperfusion injuries.
authors: School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
authors: Tristan D
authors: TD
authors: Clemons
authors: Helena M
authors: HM
authors: Viola
authors: Michael J
authors: MJ
authors: House
authors: K Swaminathan
authors: KS
authors: Iyer
authors: Livia C
authors: LC
authors: Hool
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D006168:Guinea Pigs; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D036103:Nanotechnology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D058185:Magnetite Nanoparticles; D010446:Peptide Fragments