Molecular basis for age-related changes in ileum: involvement of Bax/caspase-dependent mitochondrial apoptotic signaling.
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.
Lee
Eun Kyeong
EK
Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Jung
Kyung Jin
KJ
Choi
Jehun
J
Kim
Hyun Jung
HJ
Han
Yu Kyeong
YK
Jeong
Kyu-Shik
KS
Ji
Ae-Ri
AR
Park
Jin-Kyu
JK
Yu
Byung Pal
BP
Chung
Hae Young
HY
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*
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