Cytosolic renin is targeted to mitochondria and induces apoptosis in H9c2 rat cardiomyoblasts.
One important goal in cardiology is to prevent necrotic cell death in the heart. Necrotic cell death attracts neutrophils and monocytes into the injured myocardium. The consequences are fibrosis, remodelling and cardiac failure. The renin-angiotensin system promotes the development of cardiac failure. Recently, alternative renin transcripts have been identified lacking the signal sequence for a cotranslational transport to the endoplasmatic reticulum. These transcripts encode for a cytosolic renin with unknown functions. The expression of this alternative transcript increases after myocardial infarction. We hypothesized that cytosolic renin plays a role in survival and death of cardiomyocytes. To test this hypothesis, we overexpressed secretory or cytosolic renin in H9c2 cardiomyblasts and determined the rate of proliferation, necrosis and apoptosis. Proliferation rate, as indicated by BrdU incorporation into DNA, was reduced by secretory and cytosolic renin (cells transfected with control vector: 0.33 +/- 0.06; secretory renin: 0.12 +/- 0.02; P < 0.05; cytosolic renin: 0.15 +/- 0.03; P < 0.05). Necrosis was increased by secretory renin but decreased by cytosolic renin (LDH release after 10 days from cells transfected with control vector: 68.5 +/- 14.9; secretory renin: 100.0 +/- 0; cytosolic renin: 25.5 +/- 5.3% of content, each P < 0.05). Mitochondrial apoptosis, as indicated by phosphatidylserin translocation to the outer membrane, was unaffected by secretory renin but increased by cytosolic renin (controls: 23.8 +/- 3.9%; secretory renin: 22.1 +/- 4.7%; cytoplasmatic renin: 41.2 +/- 3.8%; P < 0.05). The data demonstrate that a cytosolic renin exists in cardiomyocytes, which in contradiction to secretory renin protects from necrosis but increases apoptosis. Non-secretory cytosolic renin can be considered as a new target for cardiac failure.
Wanka
Heike
H
Institute of Physiology, University of Greifswald, Karlsburg, Germany.
Kessler
Nicole
N
Ellmer
Janett
J
Endlich
Nicole
N
Peters
Barbara S
BS
Clausmeyer
Susanne
S
Peters
Jörg
J
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D003600:Cytosol / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005453:Fluorescence; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009336:Necrosis; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D012333:RNA, Messenger; D012083:Renin