title: Modulation of muscle contraction by a cell-permeable peptide.
abstract: In contrast to immortal cell lines, primary cells are hardly susceptible to intracellular delivery methods such as transfection. In this study, we evaluated the direct delivery of several cell-permeable peptides under noninvasive conditions into living primary adult rat cardiomyocytes. We specifically monitored the functional effects of a cell-permeable peptide containing the 15 amino acid N-terminal peptide from human ventricular light chain-1 (VLC-1) on contraction and intracellular Ca2+ signals after electrical stimulation in primary adult cardiomyocytes. The transducible VLC-1 variant was taken up by cardiomyocytes within 5 min with more than 95% efficiency and localized to sarcomeric structures. Analysis of the functional effects of the cell-permeable VLC-1 revealed an enhancement of the intrinsic contractility of cardiomyocytes without affecting the intracellular Ca2+. Therefore, peptide transduction mediated by cell-penetrating peptides represents not only a unique strategy to enhance heart muscle function with no secondary effect on intracellular Ca2+ but also an invaluable tool for the modulation and manipulation of protein interactions in general and in primary cells.
authors: Max Delbrück Center for Molecular Medicine, Robert Rössle Str. 10, 13125, Berlin, Germany.
authors: Gisela
authors: G
authors: Tünnemann
authors: Peter
authors: P
authors: Karczewski
authors: Hannelore
authors: H
authors: Haase
authors: M Cristina
authors: MC
authors: Cardoso
authors: Ingo
authors: I
authors: Morano
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006801:Humans; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism; D024723:Ventricular Myosins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D018994:Myosin Light Chains; D010446:Peptide Fragments; C076659:myosin light chain I; D024723:Ventricular Myosins
references: J Biol Chem. 2002 Aug 9;277(32):29181-6
references: 12042324
references: J Physiol. 1994 Jul 15;478 ( Pt 2):341-9
references: 7965849
references: Biol Chem. 2002 Oct;383(10):1593-9
references: 12452436
references: J Biol Chem. 2003 Jan 3;278(1):585-90
references: 12411431
references: Nucleic Acids Res. 2003 Jan 15;31(2):556-61
references: 12527762
references: Biochemistry. 2003 Aug 5;42(30):9185-94
references: 12885253
references: Circulation. 2003 Aug 19;108(7):869-75
references: 12860903
references: Blood. 2003 Sep 15;102(6):2259-67
references: 12763940
references: Biochemistry. 1995 Jul 18;34(28):8960-72
references: 7619795
references: Biochemistry. 1996 Apr 30;35(17):5404-17
references: 8611530
references: Trends Cell Biol. 1998 Feb;8(2):84-7
references: 9695814
references: Eur J Cardiothorac Surg. 2005 Jan;27(1):117-21
references: 15621482
references: J Mol Cell Cardiol. 2005 Mar;38(3):485-93
references: 15733908
references: Circulation. 2006 Mar 7;113(9):1235-43
references: 16505175
references: FASEB J. 2006 May;20(7):865-73
references: 16675844
references: FASEB J. 2006 Sep;20(11):1775-84
references: 16940149
references: J Biol Chem. 2007 Feb 9;282(6):4113-23
references: 17142835
references: J Struct Biol. 2007 Jul;159(1):158-63
references: 17498971
references: Annu Rev Biochem. 1999;68:687-728
references: 10872464
references: Cancer Res. 2001 Jan 15;61(2):474-7
references: 11212234
references: J Biol Chem. 2001 Feb 23;276(8):5836-40
references: 11084031
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11114-9
references: 11553773
references: Chem Biol. 2001 Dec;8(12):1123-9
references: 11755391
references: J Biol Chem. 2004 Mar 26;279(13):12456-61
references: 14722071
references: Mol Cell Neurosci. 2004 Oct;27(2):85-131
references: 15485768
references: Science. 1965 Oct 22;150(3695):501-3
references: 5835786
references: Biochemistry. 1984 Oct 9;23(21):4885-9
references: 6238623
references: J Virol. 1989 Jan;63(1):1-8
references: 2535718
references: Cell. 1988 Dec 23;55(6):1179-88
references: 2849509
references: Cell. 1988 Dec 23;55(6):1189-93
references: 2849510
references: J Biol Chem. 1989 Feb 5;264(4):2143-9
references: 2789520
references: J Virol. 1989 Mar;63(3):1181-7
references: 2536828
references: Genomics. 1990 Jun;7(2):289-93
references: 2129532
references: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):664-8
references: 8290579
references: J Biol Chem. 2002 Aug 16;277(33):30208-18
references: 12034749