Age-dependent modulation of NF-kappaB expression in rat adrenal gland

The current studies were initiated to examine the expression and regulation of an oxidative stress-responsive transcription factor, NF-kappa B, in rat adrenals during aging. NF- kappa B DNA-binding activity and expression of constituent proteins (Rel family of proteins and I kappa Bs) was measured in adrenal nuclear and cytoplasmic extracts from young mature (5 month) and old (24 month) Sprague-Dawley rats before and after treatment with LPS; the latter was used to further invoke oxidative stress. Administration of LPS to either young or old rats induced a dramatic activation of NF- kappa B DNA binding activity as assayed by EMSA. NF- kappa B hetero-dimers, RelA/NF- kappa B1 (p65/p50) accounted for the majority of proteins that bound to consensus NF- kappa B sequences in LPS-treated young and old animals. The intensity of DNA binding complexes was significantly reduced in old animals. The age-related decline in the activation of NF- kappa B could not be attributed to an alteration in the composition of constituent subunits or degradation of NF- kappa B inhibitory proteins (I kappa B alpha and I kappa B beta) but rather was due to selective down-regulation of RelA/p65 and NF- kappa B2/p52 proteins. No age-related or LPS-induced changes in the constitutively active transcription factors SP-1 and OCT-1 were detected. These data suggest that aberrancies in the activation of NF- kappa B DNA-binding activity may contribute to the excessive oxidative damage observed in adrenal tissue with aging and may adversely affect cellular processes crucial for intracellular cholesterol transport and steroid hormone production.