title: Molecular basis for age-related changes in ileum: involvement of Bax/caspase-dependent mitochondrial apoptotic signaling.
abstract: Previous studies indicate that in the elderly, a morphological change in the small intestine is accompanied by apoptosis. However, currently little information is available on the molecular events leading up to the apoptotic process in aged ileum. Our current study assessed mitochondrial apoptotic signaling along with key factors known to be involved in mitochondrial permeabilization in rat ileum. Experimentations were carried out utilizing Sprague-Dawley rats at 6 and 24 months of age. The histological analysis showed a significant loss in thickness of the intestinal mucosa during aging, which was accompanied by higher reactive species. Molecular analysis revealed the mitochondrial translocation of Bax showed a significant increase with aging. However, the expression of cyclophilin D, adenine nucleotide translocator, and the voltage-dependent anion channel that regulates the mitochondria permeability transition pore decreased or remained unchanged. Furthermore, the expression of caspase 3 was enhanced in aged ileum with increased DNA fragmentation, while nuclear translocation of apoptosis-inducing factor and endonuclease G were decreased with aging. In conclusion, our findings indicate that the mitochondrial translocation of Bax by increased oxidative stress may result in cell death through caspase-dependent apoptosis in aged ileum, thereby leading to a decrease in intestinal mucosal thickness during aging.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Jehun
authors.initials: J
authors.lastname: Choi
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yu Kyeong
authors.initials: YK
authors.lastname: Han
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
authors.forename: Ae-Ri
authors.initials: AR
authors.lastname: Ji
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism*; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D007082:Ileum / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D023421:Models, Animal; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D033741:Adenine Nucleotide Translocator 1; D000081406:Peptidyl-Prolyl Isomerase F; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D021983:Cyclophilins