title: Effect of a 12-month exercise intervention on the apoptotic regulating proteins Bax and Bcl-2 in colon crypts: a randomized controlled trial.
abstract: BACKGROUND
  Cellular proliferation and apoptosis (cell death) are highly regulated in the colon as insufficient apoptosis may lead to polyps and cancer. Physical activity decreases risk of colon cancer in observational studies, but the biological basis is not well defined. The objective of this study is to examine the effects of a 12-month aerobic exercise program on expression of proteins that promote (Bax) or inhibit (Bcl-2) apoptosis in colon crypts.
  
  
  METHODS
  Two hundred two sedentary participants, 40 to 75 years, were randomly assigned to moderate-to-vigorous intensity exercise for 60 min per day, 6 days per week for 12 months, or usual lifestyle. Colon crypt samples were obtained at baseline and 12 months. Bcl-2 and Bax expression was measured by immunohistochemistry.
  
  
  RESULTS
  Bax density at the bottom of crypts increased in male exercisers versus controls (+0.87 versus -0.18; P = 0.05), whereas the ratio of Bcl-2 to Bax at the bottom and middle of crypts decreased as aerobic fitness (VO(2)max) increased (P trend = 0.02 and 0.05, respectively). In female exercisers, Bax density in the middle of crypts decreased (-0.36 versus +0.69; P = 0.03) and Bcl-2 to Bax ratio at the top of crypts increased versus controls (+0.46 versus -0.85; P = 0.03). Bax density in the middle of crypts also decreased as minutes per week of exercise increased (P trend = 0.03).
  
  
  CONCLUSIONS
  A 12-month exercise intervention resulted in greater expression of proteins that promote apoptosis at the bottom of colon crypts in men and decreased expression of proteins that promote apoptosis at the middle and top of colon crypts in women. The difference in effect by gender and location of observed changes warrants further study.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Campbell
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: Shuying S
authors.initials: SS
authors.lastname: Li
authors.forename: Bess E
authors.initials: BE
authors.lastname: Sorensen
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Rudolph
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Irwin
authors.forename: Christina
authors.initials: C
authors.lastname: Surawicz
authors.forename: Kamran
authors.initials: K
authors.lastname: Ayub
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015444:Exercise; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012737:Sex Factors; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein