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MITOCHONDRIAL DYSFUNCTION IN THE AGING HEART IS ACCOMPANIED BY CONSTITUTIVE NO-SYNTHASES UNCOUPLING ON THE BACKGROUND
Fiziolohichnyi Zhurnal (Kiev, Ukraine : 1994)
|March 15, 2018
Summary
Aging increases heart mitochondrial sensitivity to calcium by reducing protective nitric oxide and hydrogen sulfide, while boosting damaging reactive oxygen and nitrogen species. This age-related oxidative and nitrosative stress impacts mitochondrial function.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Aging Research
Background:
- Mitochondrial permeability transition pore (MPTP) opening is a critical event in cell death.
- Oxidative and nitrosative stress are implicated in aging and cardiovascular dysfunction.
- Calcium overload is a primary inducer of MPTP opening.
Purpose of the Study:
- To investigate the impact of aging on MPTP sensitivity to calcium.
- To assess oxidative and nitrosative stress markers in adult and old rat hearts.
- To determine the role of nitric oxide and hydrogen sulfide in age-related mitochondrial changes.
Main Methods:
- Measurement of reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation.
- Analysis of lipid peroxidation products and urea levels.
- Assessment of nitric oxide synthase (NOS) coupling and activity, including inducible NOS (iNOS).
- Quantification of hydrogen sulfide (H2S) levels in heart mitochondria.
Main Results:
- Old rat hearts exhibited significantly increased ROS (superoxide, hydroxyl radicals) and RNS production.
- Markers of oxidative stress (urea, conjugated dienes) and nitrosative stress (nitrate reductase, iNOS activity) were elevated with age.
- Constitutive NOS (cNOS) coupling decreased, leading to reduced nitric oxide (NO) and hydrogen sulfide (H2S) levels.
- Heart mitochondria from old rats showed increased sensitivity of MPTP to calcium.
Conclusions:
- Aging exacerbates oxidative and nitrosative stress in rat hearts.
- Reduced levels of endogenous inhibitors (NO, H2S) and increased inducers (ROS, RNS) of MPTP contribute to its heightened sensitivity in aged hearts.
- Impaired cNOS coupling is a key factor in the age-associated increase in oxidative stress and MPTP sensitivity.
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