Metalloporphyrins improve the survival of Sod2-deficient neurons |
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Authors: | Patel Manisha N |
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Affiliation: | Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center and Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA |
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Abstract: | The objective of this study was to determine whether metalloporphyrin catalytic antioxidants influence the survival of neuronal cultures in an in vitro model of age-related mitochondrial oxidative stress. Neuronal cultures were prepared from cerebral cortices of manganese superoxide dismutase (MnSOD or Sod2) knockout (homozygous -/-, heterozygous -/+ or wild-type +/+) mice. The ability of catalytic antioxidants, manganese tetrakis-(4-benzoic acid) porphyrin (MnTBAP) and manganese tetrakis-(N-ethyl-2-pyridyl) porphyrin (MnTE-2-PyP) to influence the survival of cultured cerebrocortical neurones from Sod2-replete (+/+) and Sod2-deficient (+/- or -/-) mice was assessed. Sod2-/- cultures showed accelerated cell death in serum-free conditions when grown in ambient oxygen. MnTBAP and MnTE-2-PyP delayed the death of Sod2-/- cultures and improved the survival of Sod2+/+ and Sod2+/- cultures in serum-free conditions. The results suggest that metalloporphyrin antioxidants can delay neuronal death resulting specifically from increased mitochondrial oxidative stress. Furthermore, Sod2-deficient neuronal cultures provide a simple model system to screen the biological efficacy of mitochondrial antioxidants. |
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Keywords: | knockout mouse manganese superoxide dismutase (Sod2) metalloporphyrin mitochondria neuronal survival superoxide |
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