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Protection of DNA damage by dietary restriction. 总被引:5,自引:0,他引:5
Dietary restriction is known to retard the aging processes and delay the onset of age-related neoplastic diseases. The mechanisms underlying these remarkable actions of nutritional intervention are not known in spite of recently intensified research efforts. However, the last couple of years' research on dietary restriction produced strong evidence indicating that its effective antiaging actions might be related to its ability to modulate free radical damage. In the present study, DNA damage and attenuation of the damage by dietary restriction were assessed by measuring 8-hydroxydeoxyguanosine 8-OH dG) in both nuclear DNA (nuDNA) and mitochondrial DNA (mitDNA) fractions. The data show that substantially more damage (approximately 15 times) occurred in mitDNA compared to nuDNA. More interestingly, the DNA damage was significantly attenuated in dietarily restricted rats. 相似文献
84.
Fenster SD Chung WJ Zhai R Cases-Langhoff C Voss B Garner AM Kaempf U Kindler S Gundelfinger ED Garner CC 《Neuron》2000,25(1):203-214
Piccolo is a novel component of the presynaptic cytoskeletal matrix (PCM) assembled at the active zone of neurotransmitter release. Analysis of its primary structure reveals that Piccolo is a multidomain zinc finger protein structurally related to Bassoon, another PCM protein. Both proteins were found to be shared components of glutamatergic and GABAergic CNS synapses but not of the cholinergic neuromuscular junction. The Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. We show that PRA1 is a synaptic vesicle-associated protein that is colocalized with Piccolo in nerve terminals of hippocampal primary neurons. These data suggest that Piccolo plays a role in the trafficking of synaptic vesicles (SVs) at the active zone. 相似文献
85.
Dingge Ying Pak Chung Sham David Keith Smith Lu Zhang Yu Lung Lau Wanling Yang 《Genome biology》2015,16(1)
Recent founder mutations may play important roles in complex diseases and Mendelian disorders. Detecting shared haplotypes that are identical by descent (IBD) could facilitate discovery of these mutations. Several programs address this, but are usually limited to detecting pair-wise shared haplotypes and not providing a comparison of cases and controls. We present a novel algorithm and software package, HaploShare, which detects extended haplotypes that are shared by multiple individuals, and allows comparisons between cases and controls. Testing on simulated and real cases demonstrated significant improvements in detection power and reduction of false positive rate by HaploShare relative to other programs.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-015-0662-9) contains supplementary material, which is available to authorized users. 相似文献86.
Zhigang Jin Jin Wei Chung Wenyan Mei Stefan Strack Chunyan He Gee W. Lau Jing Yang 《Molecular biology of the cell》2015,26(6):1160-1173
Recent genome-wide association studies reveal that the FAM13A gene is associated with human lung function and a variety of lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary fibrosis. The biological functions of Fam13a, however, have not been studied. In an effort to identify novel substrates of B56-containing PP2As, we found that B56-containing PP2As and Akt act antagonistically to control reversible phosphorylation of Fam13a on Ser-322. We show that Ser-322 phosphorylation acts as a molecular switch to control the subcellular distribution of Fam13a. Fam13a shuttles between the nucleus and cytoplasm. When Ser-322 is phosphorylated by Akt, the binding between Fam13a and 14-3-3 is enhanced, leading to cytoplasmic sequestration of Fam13a. B56-containing PP2As dephosphorylate phospho–Ser-322 and promote nuclear localization of Fam13a. We generated Fam13a-knockout mice. Fam13a-mutant mice are viable and healthy, indicating that Fam13a is dispensable for embryonic development and physiological functions in adult animals. Intriguingly, Fam13a has the ability to activate the Wnt pathway. Although Wnt signaling remains largely normal in Fam13a-knockout lungs, depletion of Fam13a in human lung cancer cells causes an obvious reduction in Wnt signaling activity. Our work provides important clues to elucidating the mechanism by which Fam13a may contribute to human lung diseases. 相似文献
87.
Vazhaikkurichi M. Rajendran Navalpur S. Nanda Kumar Chung M. Tse Henry J. Binder 《The Journal of biological chemistry》2015,290(42):25487-25496
Diarrhea associated with ulcerative colitis (UC) occurs primarily as a result of reduced Na+ absorption. Although colonic Na+ absorption is mediated by both epithelial Na+ channels (ENaC) and Na-H exchangers (NHE), inhibition of NHE-mediated Na+ absorption is the primary cause of diarrhea in UC. As there are conflicting observations reported on NHE expression in human UC, the present study was initiated to identify whether NHE isoforms (NHE2 and NHE3) expression is altered and how Na+ absorption is regulated in DSS-induced inflammation in rat colon, a model that has been used to study UC. Western blot analyses indicate that neither NHE2 nor NHE3 expression is altered in apical membranes of inflamed colon. Na+ fluxes measured in vitro under voltage clamp conditions in controls demonstrate that both HCO3−-dependent and butyrate-dependent Na+ absorption are inhibited by S3226 (NHE3-inhibitor), but not by HOE694 (NHE2-inhibitor) in normal animals. In contrast, in DSS-induced inflammation, butyrate-, but not HCO3−-dependent Na+ absorption is present and is inhibited by HOE694, but not by S3226. These observations indicate that in normal colon NHE3 mediates both HCO3−-dependent and butyrate-dependent Na+ absorption, whereas DSS-induced inflammation activates NHE2, which mediates butyrate-dependent (but not HCO3−-dependent) Na+ absorption. In in vivo loop studies HCO3−-Ringer and butyrate-Ringer exhibit similar rates of water absorption in normal rats, whereas in DSS-induced inflammation luminal butyrate-Ringer reversed water secretion observed with HCO3−-Ringer to fluid absorption. Lumen butyrate-Ringer incubation activated NHE3-mediated Na+ absorption in DSS-induced colitis. These observations suggest that the butyrate activation of NHE2 would be a potential target to control UC-associated diarrhea. 相似文献
88.
Hyun-Jin Shin Eun-Ran Park Sun-Hee Yun Su-Hyeon Kim Won-Hee Jung Seon Rang Woo Hyun-Yoo Joo Su Hwa Jang Hee Yong Chung Sung Hee Hong Myung-Haing Cho Joong-Jean Park Miyong Yun Kee-Ho Lee 《PloS one》2015,10(11)
Mad2, a key component of the spindle checkpoint, is closely associated with chromosomal instability and poor prognosis in cancer. p31comet is a Mad2-interacting protein that serves as a spindle checkpoint silencer at mitosis. In this study, we showed that p31comet-induced apoptosis and senescence occur via counteraction of Mad2 activity. Upon retroviral transduction of p31comet, the majority of human cancer cell lines tested lost the ability to form colonies in a low-density seeding assay. Cancer cells with p31comet overexpression underwent distinct apoptosis and/or senescence, irrespective of p53 status, confirming the cytotoxicity of p31comet. Interestingly, both cytotoxic and Mad2 binding activities were eliminated upon deletion of the C-terminal 30 amino acids of p31comet. Point mutation or deletion of the region affecting Mad2 binding additionally abolished cytotoxic activity. Consistently, wild-type Mad2 interacting with p31comet, but not its non-binding mutant, inhibited cell death, indicating that the mechanism of p31comet-induced cell death involves Mad2 inactivation. Our results clearly suggest that the regions of p31comet affecting interactions with Mad2, including the C-terminus, are essential for induction of cell death. The finding that p31comet-induced cell death is mediated by interactions with Mad2 that lead to its inactivation is potentially applicable in anticancer therapy. 相似文献
89.
90.
Itoh S Saito T Hirata M Ushita M Ikeda T Woodgett JR Algül H Schmid RM Chung UI Kawaguchi H 《The Journal of biological chemistry》2012,287(35):29227-29236