The synthetic antimicrobial peptide 19-2.5 attenuates mitochondrial dysfunction in cardiomyocytes stimulated with human sepsis serum.
Septic cardiomyopathy affects up to 70% of patients with septic shock and the derangement of cardiac mitochondrial function contributes to the likelihood of death. However, at present, there is no specific therapeutic drug available. The peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) and coactivator-1β (PGC-1β) modulate members of the PPARs, which regulate mitochondrial energy metabolism and the production of mitochondrial reactive oxygen species in the heart. This study investigated the potential of the newly developed synthetic antimicrobial peptide 19-2.5 (Pep2.5) to attenuate mitochondrial dysfunction in murine cardiomyocytes stimulated with serum from septic shock patients. Pep2.5 treatment attenuated the suppression of PPAR-α, PPAR-γ ( P = 0.0004 and P = 0.0001, respectively) and PGC-1α/β ( P = 0.0008 and P = 0.0147, respectively) in cardiomyocytes stimulated with serum from septic shock patients compared with untreated cells. Pep2.5 treatment enhanced the mitochondrial maximum respiration ( P < 0.0001), increased cellular ATP levels ( P < 0.0001) and reduced the production of mitochondrial reactive oxygen species. Thus, the administration of Pep2.5 may have the potential as a promising therapeutic approach in septic cardiomyopathy by attenuating mitochondrial dysfunction in the septic heart.
1 Department of Intensive Care and Intermediate Care, University Hospital Aachen, Aachen, Germany.
Lukas
L
Martin
1 Department of Intensive Care and Intermediate Care, University Hospital Aachen, Aachen, Germany.
Carsten
C
Peters
2 Clinical and Experimental Pathology, Forschungszentrum Borstel, Borstel, Germany.
Lena
L
Heinbockel
3 Department of Cardiology, Pneumology, Angiology and Intensive Care, University Hospital Aachen, Aachen, Germany.
Julia
J
Moellmann
4 Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany.
Antons
A
Martincuks
5 Division of Biophysics, Forschungszentrum Borstel, Borstel, Germany.
Klaus
K
Brandenburg
4 Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany.
Michael
M
Lehrke
4 Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany.
Gerhard
G
Müller-Newen
1 Department of Intensive Care and Intermediate Care, University Hospital Aachen, Aachen, Germany.
Gernot
G
Marx
1 Department of Intensive Care and Intermediate Care, University Hospital Aachen, Aachen, Germany.
Tobias
T
Schuerholz
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D015850:Interleukin-6; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha
HL-1 cells; Septic cardiomyopathy; antimicrobial peptide; mitochondrial reactive oxygen species