Open AccessMetalloporphyrins improve the survival of Sod2 ‐deficient neurons
Author(s) -
Patel Manisha N.
Publication year - 2003
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1046/j.1474-9728.2003.00055.x
Subject(s) - sod2 , oxidative stress , sod1 , mitochondrion , biology , superoxide dismutase , reactive oxygen species , programmed cell death , apoptosis , in vitro , oxidative phosphorylation , mitochondrial ros , biochemistry , microbiology and biotechnology
Summary 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.