SRF BINDING TO SRE IN THE RAT-HEART - INFLUENCE OF AGE

One important promoter element at the 5' end of the c-fos gene is the serum response element (SRE). SRE is the site of attachment of the 67- kDa protein serum response factor (SRF) and several accessory proteins (Elk1, SAP1, SAP2/NET) termed the ternary complex factors. The bindin g of SRF to SRE plays art integral role in c-fos transcription and may occur independently of the association of the ternary complex factors . In the current study, we found that SRF protein expression was incre ased in the hearts of the old vs young adult rats in the basal conditi on. The hearts of old rats may have posttranslationally modified SRF p roteins that are different compared to that of the young adults. The S RF increase was present both in the cytoplasm as well as in the nucleu s in the old hearts. To test whether SRF protein levels in response to acute stress might be altered with age, we studied hearts of young ad ult and old rats during myocardial infarction. The young adult rat hea rts responded to acute ischemic stress with an increase ill both p62 a nd p67 SRF. The hearts of the old rats, however, did not exhibit a sig nificant change in SRF protein expression. These findings demonstrate qualitative as well as quantitative age differences in SRF protein lev els, both at baseline and following stimulation. The reduced SRF expre ssion in response to acute cardiac ischemic stress in the old rats mig ht contribute to the observed age-related decrease in the induction of immediate early genes such as c-fos in the heart.