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Altered Mitochondrial Morphology Elucidates Cell Death Mechanisms in the Aged Female Rat Heart
Author(s) -
Diaz Carlos,
Machikas Alexandra,
Ball Richard W,
Lopez Veronica,
Korzick Donna H
Publication year - 2013
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.27.1_supplement.1194.6
Subject(s) - dna laddering , tunel assay , necrosis , apoptosis , programmed cell death , medicine , endocrinology , biology , mitochondrion , mitochondrial dna , autophagy , andrology , microbiology and biotechnology , genetics , dna fragmentation , gene
Background Acute myocardial infarction and associated ischemia/reperfusion (I/R) injury remains a leading cause of death in older post‐menopausal women. I/R injury triggers mitochondrial dysfunction leading to necrosis, apoptosis, and/or autophagy. Purpose To determine if age‐associated estrogen deficiency alters mitochondrial morphology in conjunction with vulnerability to I/R injury. Methods Mitochondrial morphology was assessed through electron microscopy in border zone regions following coronary artery ligation (55 min I and 4–6 hr R) or sham in adult (6 mo) ovary‐intact, aged (24 mo) ovary‐intact and aged ovariectomized (OVX) female F344 rats. Necrosis was assessed by triphenyltetrazolium chloride staining, apoptosis by DNA laddering and TUNEL, and markers of autophagy by western blotting. Results Loss of mitochondrial matrix following I/R was greatest in aged OVX. Mitochondrial area was less in aged vs adult in conjunction with increased mitochondrial number and marked Z line streaming. Reduced DNA laddering and TUNEL, combined with increased beclin‐1 and cathepsinD in aged vs adult, further support a dominant role for necrosis underlying cell death in aged females (n=4–5/group). Conclusion Morphological alterations in mitochondria with aging are likely contributory in necrotic cell death mechanisms associated with I/R injury in post‐menopausal women.