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Differential Effects of Aging on MCL‐1 And Caspase 3 Expression in Murine Small And Large Intestine
Author(s) -
Reddix Rhoda A,
Hans Chetan,
Boulares Hamid,
Lucchesi Pamela A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a808-d
Subject(s) - apoptosis , cytochrome c , caspase 3 , caspase , biology , caspase 9 , microbiology and biotechnology , programmed cell death , cancer research , chemistry , biochemistry
Background: MCL‐1, myeloid cell leukaemia‐1, is a pro‐survival protein expressed in differentiated cells. It is cleaved by caspase 3 and induces apoptosis in terminally differentiated cells. Several reports describe an aging‐related decline in the apoptosis of terminally differentiated intestinal epithelia, which may lead to a precancerous state. Aim: To investigate the effect of aging on apoptotic proteins within murine intestinal tissues and corresponding changes in MCL‐1 expression. Methods: Young 3–4 mo. and aged 18–20 mo. C57BL/6 mice (n=3) were sacrificed, both ileal and colonic segments were fixed in 4% paraformaldehyde and processed for immunohistochemical analysis of cytochrome c (Cyto c), apoptosis inducing factor (AIF), caspase 3 and MCL‐1 long expression. Results: In all tissues, cyto c, AIF, cleaved caspase 3 and MCL‐1 were only expressed in differentiated cells. The expression patterns and intensity of pro‐apoptotic proteins and MCL‐1 were unaltered with aging in ileal tissues. Although cyto C and AIF were unaltered in colonic tissues, caspase 3 expression was reduced and MCL‐1 expression was enhanced in aged mice. Conclusion: The data suggest that apoptosis is differentially regulated in murine intestine during aging. Furthermore, the decline in apoptosis may be due to aberrant changes in the regulation of MCL‐1 expression and caspase‐3 dependent degradation. Supported by NIH P20RR18766.