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Cardioprotection in iNOS transgenic mice is independent of mitochondrial biogenesis.
Author(s) -
Keith Rachel,
Hill Bradford,
Conklin Daniel J,
Bolli Roberto,
Bhatnagar Aruni
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.835.2
Subject(s) - mitochondrial permeability transition pore , cardioprotection , mitochondrial biogenesis , nitric oxide synthase , mitochondrial dna , mitochondrion , atp synthase , genetically modified mouse , chemistry , microbiology and biotechnology , biology , nitric oxide , apoptosis , transgene , biochemistry , medicine , endocrinology , programmed cell death , ischemia , enzyme , gene
Inducible nitric oxide synthase (iNOS) is a known mediator of the late phase ischemic preconditioning (PC) against myocardial infarction. We have found that cardiac‐specific iNOS transgenic mice are protected from ischemic injury. It is also known that NO donors trigger PC by increasing iNOS and that they stimulate mitochondrial biogenesis. We hypothesize that protection by iNOS is linked to an increase in mitochondrial biogenesis. Mitochondrial density was examined by transmission microscopy of left papillary muscle from iNOS‐TG or wild type (WT) mice. No significant difference in mitochondrial count or size distribution was observed. Citrate synthase activity was not significantly different between iNOS‐TG and WT hearts. There was also no significant difference in the ratio of the mitochondrial DNA to the genomic DNA of iNOS‐TG or WT mice when compared cytochrome b primers with GAPDH using quantitative PCR or PCR. No difference in the levels of mitochondrial proteins cytochrome c , CcO‐IV was observed between iNOS‐TG and WT hearts. Addition of NO donors decreased ΔΨ and prevented permeability transition in mitochondria isolated from either WT or iNOS‐TG hearts. We conclude that overexpression of iNOS does not induce mitochondrial biogenesis and that cardioprotection due to iNOS may be related directly to the ability of NO to prevent mitochondrial permeability transition and subsequent activation of cell death. This work was supported by NIH grants HL5547 (to A.B) and HL78825 (to R.B.)