Metalloporphyrins improve the survival of Sod2-deficient neurons.
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.
Patel
Manisha N
MN
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center Denver, CO 80262, USA. manisha.patel@uchsc.edu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D016895:Culture Media, Serum-Free; D008665:Metalloporphyrins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin