Melusin Promotes a Protective Signal Transduction Cascade in Stressed Hearts.
Melusin is a chaperone protein selectively expressed in heart and skeletal muscles. Melusin expression levels correlate with cardiac function in pre-clinical models and in human patients with aortic stenosis. Indeed, previous studies in several animal models indicated that Melusin plays a broad cardioprotective role in different pathological conditions. Chaperone proteins, besides playing a role in protein folding, are also able to facilitate supramolecular complex formation and conformational changes due to activation/deactivation of signaling molecules. This role sets chaperone proteins as crucial regulators of intracellular signal transduction pathways. In particular Melusin activates AKT and ERK1/2 signaling, protects cardiomyocytes from apoptosis and induces a compensatory hypertrophic response in several pathological conditions. Therefore, selective delivery of the Melusin gene in heart via cardiotropic adenoviral associated virus serotype 9 (AAV9), may represent a new promising gene-therapy approach for different cardiac pathologies.
Department of Molecular Biotechnology and Health Sciences, University of Torino Torino, Italy.
Matteo
M
Sorge
Department of Molecular Biotechnology and Health Sciences, University of Torino Torino, Italy.
Mara
M
Brancaccio
AKT; ERK 1/2; HSP90; Melusin; apoptosis; chaperone; heart failure; intracellular signaling
FEBS Lett. 2002 Oct 9;529(2-3):162-7
12372593
Biochim Biophys Acta. 2012 Mar;1823(3):674-82
21945180
Front Cardiovasc Med. 2015 May 19;2:25
26664897
Cardiovasc Res. 2014 Jun 1;102(3):346-61
24585203
Lancet. 2014 May 31;383(9932):1933-43
24831770
Autophagy. 2011 Jan;7(1):101-3
21045566
Biochemistry. 2008 Jul 8;47(27):7001-11
18557634
FEBS Lett. 2008 Jun 11;582(13):1788-94
18474241
J Mol Biol. 2015 Apr 10;427(7):1537-48
25681016
Cardiovasc Pathol. 2012 Mar-Apr;21(2):105-11
21546274
Mol Cell. 2010 Jul 30;39(2):269-81
20670895
Cardiovasc Res. 2004 Feb 15;61(3):448-60
14962476
Biochim Biophys Acta. 2012 Mar;1823(3):624-35
21951723
BMC Med Genet. 2009 Dec 17;10:140
20017903
J Biol Chem. 1999 Oct 8;274(41):29282-8
10506186
Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2324-32
17220194
World J Cardiol. 2011 Jun 26;3(6):186-200
21772945
Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1435-41
15178564
Trends Mol Med. 2003 Sep;9(9):376-82
13129703
Int J Biochem Cell Biol. 2012 Oct;44(10):1632-45
22710345
Science. 2016 Jul 1;353(6294):aac4354
27365453
Cardiovasc Res. 2004 Aug 15;63(3):373-80
15276462
FEBS Lett. 2005 Aug 15;579(20):4513-9
16083881
Cardiovasc Res. 2011 Aug 1;91(3):456-64
21493702
Biochimie. 2016 Aug;127:227-40
27295069
J Clin Invest. 2013 Jan;123(1):46-52
23281409
Hum Gene Ther. 1997 Feb 10;8(3):275-84
9048194
Biochim Biophys Acta. 2015 Apr;1854(4):291-319
25556000
J Biol Chem. 2004 Apr 16;279(16):16511-7
14761955
Gene Ther. 1999 Sep;6(9):1574-83
10490767
Circulation. 2010 Oct 26;122(17):1740-51
20975010
Basic Res Cardiol. 2014 Jul;109 (4):418
24859929
J Biol Chem. 2011 Sep 2;286(35):30837-46
21757757
Mol Cell Proteomics. 2010 Feb;9(2):255-70
19875381
Cardiovasc Res. 2014 Jan 1;101(1):97-107
24130190
Circ Res. 2003 Jun 27;92 (12 ):e87-100
12775586
Biochim Biophys Acta. 2016 Jan;1860(1 Pt B):222-33
26365509
J Biol Chem. 2013 Jan 4;288(1):215-22
23184943
J Mol Cell Cardiol. 2011 Oct;51(4):574-7
20869365
Cell. 1999 Nov 12;99(4):355-66
10571178
Circ Res. 2015 May 22;116(11):1863-82
25999425
Proteomics Clin Appl. 2014 Aug;8(7-8):534-42
24946239
Biochem Soc Trans. 2014 Apr;42(2):270-3
24646229
J Cell Sci. 2011 Oct 15;124(Pt 20):3515-24
22010199
Int J Biochem Cell Biol. 2012 Oct;44(10):1588-92
22449631
J Mol Cell Cardiol. 2005 Jan;38(1):47-62
15623421
Gene. 2013 Jan 10;512(2):206-10
23124043
Cardiovasc Res. 2006 Jun 1;70(3):422-33
16466704
N Engl J Med. 2007 Sep 13;357(11):1121-35
17855673
Circ Res. 2005 May 27;96(10 ):1087-94
15860758
Prog Biophys Mol Biol. 2014 Jul;115(1):3-10
24576798
Eur J Heart Fail. 2007 Jun-Jul;9(6-7):568-73
17468044
Cell Mol Life Sci. 2013 Nov;70(21):4047-54
23532408
Nat Med. 2003 Jan;9(1):68-75
12496958
N Engl J Med. 2013 Jan 31;368(5):455-64
23363499