AIMS: @entity28 and @entity6 ( @entity6 ) frequently coexist and increase the propensity of @entity65 by numerous mechanisms. Chief among them are oxidative stress and @entity141 dysregulation, and both are inducers of the mitochondrial permeability transition pore (MPTP). Nevertheless, it is unknown whether MPTP formation is triggered in @entity6 animals, and thereby contributing to @entity299 . We assessed MPTP sensitivity and reactive @entity26 species production in cardiac mitochondria, as well as cytosolic @entity141 handling in ventricular myocytes from @entity35 with @entity6 . MAIN METHODS: Male Zucker Fa/fa @entity35 (Fa/fa) 32weeks old presenting @entity6 , @entity1184 , and @entity67 were used. MPTP formation was evaluated in isolated mitochondria and @entity141 handling in ventricular myocytes, by spectrophotometric and confocal microscope techniques, respectively. KEY FINDINGS: We found that the systolic @entity141 transient relaxation was ~40% slower, while mitochondrial @entity5568 production increased by ~6-fold. MPTP opening in isolated mitochondria from Fa/fa (mFa/fa) was more sensitive to @entity141 than in mitochondria from lean @entity35 (mLean), and correlated with increased @entity1432 groups exposure. The mFa/fa showed decreased oxidative phosphorylation capacity. The @entity855 content decreased in myocytes, while the PCr/ @entity855 ratio remained unchanged and @entity2311 activity largely increased in myocytes from Fa/fa animals. SIGNIFICANCE: Our results showed that oxidative stress and diastolic @entity141 dysregulation increased MPTP sensitivity leading to @entity2383 and apoptosis. Mitochondrial dysfunction could compromise @entity855 synthesis, and lower @entity855 could be linked to decreased @entity11474 activity, which might underlie @entity67 . Prolonged @entity141 transients might further exacerbate @entity2383 .

Enhanced oxidative stress sensitizes the mitochondrial permeability transition pore to opening in heart from zucker Fa/fa @entity35 with type 2 XXXX .

@entity5568 :: ('D006861', 'Chemical') :: ['H2O2'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes mellitus type 2', 'DM2'] @entity28 :: ('MESH:D009765', 'Disease') :: ['Obesity'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['concentric hypertrophy'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity11474 :: ('29693(Tax:10116)', 'Gene') :: ['SERCA2'] @entity2311 :: ('58918(Tax:10116)', 'Gene') :: ['caspase 9'] @entity1432 :: ('CHEBI:29256', 'Chemical') :: ['thiol'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac dysfunction'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity67 :: ('MESH:D018754', 'Disease') :: ['diastolic dysfunction'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular dysfunction'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial dysfunction']
@entity6 :: (MESH:D003920,Disease) :: ['diabetes']
