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71.
Short‐term hypoxia upregulated Mas receptor expression to repress the AT1R signaling pathway and attenuate Ang II‐induced cardiomyocyte apoptosis 下载免费PDF全文
72.
Dennis J. Bua Alex J. Kuo Peggie Cheung Chih Long Liu Valentina Migliori Alexsandra Espejo Fabio Casadio Christian Bassi Bruno Amati Mark T. Bedford Ernesto Guccione Or Gozani 《PloS one》2009,4(8)
Knowledge of protein domains that function as the biological effectors for diverse post-translational modifications of histones is critical for understanding how nuclear and epigenetic programs are established. Indeed, mutations of chromatin effector domains found within several proteins are associated with multiple human pathologies, including cancer and immunodeficiency syndromes. To date, relatively few effector domains have been identified in comparison to the number of modifications present on histone and non-histone proteins. Here we describe the generation and application of human modified peptide microarrays as a platform for high-throughput discovery of chromatin effectors and for epitope-specificity analysis of antibodies commonly utilized in chromatin research. Screening with a library containing a majority of the Royal Family domains present in the human proteome led to the discovery of TDRD7, JMJ2C, and MPP8 as three new modified histone-binding proteins. Thus, we propose that peptide microarray methodologies are a powerful new tool for elucidating molecular interactions at chromatin. 相似文献
73.
Chemiluminescence analysis of antioxidant capacity for serum albumin isolated from healthy or uremic volunteers 下载免费PDF全文
Chih‐Yang Huang Show‐Yih Liou Wei‐Wen Kuo Hsi‐Chin Wu Yen‐Lin Chang Tung‐Sheng Chen 《Luminescence》2016,31(8):1474-1478
Regular hemodialysis treatment induces an elevation in oxidative stress in patients with end‐stage renal failure, resulting in oxidative damage of the most abundant serum protein, albumin. Oxidation of serum albumin causes depletion of albumin reactive thiols, leading to oxidative modification of serum albumin. The aim of this study was to screen the antioxidant capacity of albumins isolated from uremic patients (HD‐ALB) or healthy volunteers (N‐ALB). From high‐performance liquid chromatography spectra, we observed that one uremic solute binds to HD‐ALB via the formation of disulfide bonds between HD‐ALB and the uremic solute. Furthermore, we found using chemiluminescent analysis that the antioxidant capacities for N‐ALB to scavenge reactive oxygen species including singlet oxygen, hypochlorite and hydrogen peroxide were higher than HD‐ALB. Our results suggest that protein‐bound uremic solute binds to albumin via formation of disulfide bonds, resulting in the depletion of albumin reactive thiols. The depletion of albumin reactive thiols leads to a reduced antioxidant capacity of HD‐ALB, implying postmodification of albumin. This situation may reduce the antioxidant capacity of albumin and increase oxidative stress, resulting in increase in complications related to oxidative damage in uremic patients. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
74.
Tzung-Ju Wu Yi-Hsuan Chiang Yi-Chien Lin Chang-Ru Tsai Tai-Yuan Yu Ming-Ta Sung Yan-Hwa Wu Lee Jing-Jer Lin 《The Journal of biological chemistry》2009,284(19):12801-12808
Ku is a heterodimeric protein involved in nonhomologous end-joining of the
DNA double-stranded break repair pathway. It binds to the double-stranded DNA
ends and then activates a series of repair enzymes that join the broken DNA.
In addition to its function in DNA repair, the yeast Saccharomyces
cerevisiae Ku (Yku) is also a component of telomere protein-DNA complexes
that affect telomere function. The yeast telomeres are composed of duplex
C1–3(A/T)G1–3 telomeric DNA repeats plus
single-stranded TG1–3 telomeric DNA tails. Here we show that
Yku is capable of binding to a tailed-duplex DNA formed by telomeric DNA that
mimics the structure of telomeres. Addition of Cdc13p, a single-stranded
telomeric DNA-binding protein, to the Yku-DNA complex enables the formation of
a ternary complex with Cdc13p binding to the single-stranded tail of the DNA
substrate. Because pre-loading of Cdc13p to the single-stranded telomeric tail
inhibits the binding of Yku, the results suggested that loading of Yku and
Cdc13p to telomeres is sequential. Through generating a double-stranded break
near telomeric DNA sequences, we found that Ku protein appears to bind to the
de novo synthesized telomeres earlier than that of Cdc13p in
vivo. Thus, our results indicated that Yku interacts directly with
telomeres and that sequential loading of Yku followed by Cdc13p to telomeres
is required for both proteins to form a ternary complex on telomeres. Our
results also offer a mechanism that the binding of Cdc13p to telomeres might
prevent Yku from initiating DNA double-stranded break repair pathway on
telomeres.DNA damages in the form of double-stranded breaks
(DSBs)4 compromise the
integrity of genomes. Failure in repairing or mis-repairing double-stranded
breaks can lead to chromosome instability and eventually cell death or cancer
(1). Double-stranded breaks are
repaired by two main pathways, the homologous recombination and nonhomologous
DNA end-joining. In nonhomologous DNA end-joining, Ku is the first protein to
bind to the DNA ends to initiate the repair pathway
(2). Upon binding, Ku then
recruits a series of repair enzymes to join the broken ends
(2). Ku is a heterodimeric
protein composed of 70- and ∼80-kDa subunits. In Saccharomyces
cerevisiae, Ku includes Yku70 and Yku80 subunits. Because the biochemical
configuration of the broken ends could be very diverse on DSBs, Ku binds to
double-stranded ends in a sequence- and energy-independent manner. It is
capable of binding to DNA ends with blunt 3′-overhangs or
5′-overhangs as well as double-stranded DNA with nicks, gaps, or
internal loops
(3–7).
However, Ku does not have high affinity to single-stranded DNA. The crystal
structure of human Ku heterodimer indicates that it forms a ring structure
that encircles duplex DNA (7).
This unique structure feature enables Ku to recognize DNA ends and achieves
its high affinity binding.In additional to the role in double-stranded break repair, Ku was shown to
be a component of telomeric protein-DNA complex in yeast and mammals
(8–10).
Telomeres are terminal structures of chromosomes composed of short tandem
repeated sequences (11,
12). Mutation of
YKU70 or YKU80 causes defects in telomere structure
(13–15),
telomere silencing
(16–19),
and replication timing of telomeres
(20). The function of yeast Ku
(Yku) on telomeres could mediate through protein-protein interaction with
Sir4p or protein-RNA interaction with Tlc1 RNA
(21,
22). For example, through the
interaction with Sir4p, Yku selectively affects telomeres silencing but not
the silent mating type loci
(17). Yku could also bind to
telomerase Tlc1 RNA for telomere length maintenance
(22). Judged by the DNA
binding activity of Yku, it is reasonable to suggest that it may bind directly
to telomeric DNA. Indeed, it was shown that human Ku is capable of binding
directly to telomeric DNA in vitro
(15). Moreover, because the
deletion of SIR4 in budding yeast
(23) or Taz1 in
fission yeast (24) does not
abolish the association of Ku with chromosomal ends, this suggests that Ku
might bind directly to telomeric DNA in cells. However, because yeast
telomeres have a short 12–14-mer single-stranded tail
(25), it is uncertain whether
Yku could pass the single-stranded region to reach its binding site. The
direct binding of Yku to telomeric DNA has not been experimentally
determined.In contrast to double-stranded breaks, the ends of linear chromosomes are
not recognized by repair enzymes as DNA damage. In S. cerevisiae,
Cdc13p is the single-stranded TG1–3 DNA-binding protein that
enables cells to differentiate whether the ends of a linear DNA are telomeres
or broken ends
(26–29).
Thus, although the mechanism of how cells prevent the activation of DSB repair
pathway in telomere is unclear, it is likely that binding of Cdc13p to
telomeres might inhibit the initiation of DNA damage response by the Ku
protein. Here, using a tailed-duplex DNA synthesized by telomeric DNA
sequences to mimic telomere structure, we showed that Yku binds directly to
this tailed-duplex DNA substrate and forms a ternary complex with Cdc13p. Our
results also showed that Yku loaded to a de novo synthesized telomere
earlier than Cdc13p in vivo. These results support the direct binding
of Yku to telomeric DNA and that the spatial orientation of Cdc13p might block
the activation of DSB repair pathway on telomeres. 相似文献
75.
Xiaodong Mu Chieh Tseng William S. Hambright Polina Matre Chih‐Yi Lin Palas Chanda Wanqun Chen Jianhua Gu Sudheer Ravuri Yan Cui Ling Zhong John P. Cooke Laura J. Niedernhofer Paul D. Robbins Johnny Huard 《Aging cell》2020,19(8)
Hutchinson–Gilford progeria syndrome (HGPS) is caused by the accumulation of mutant prelamin A (progerin) in the nuclear lamina, resulting in increased nuclear stiffness and abnormal nuclear architecture. Nuclear mechanics are tightly coupled to cytoskeletal mechanics via lamin A/C. However, the role of cytoskeletal/nuclear mechanical properties in mediating cellular senescence and the relationship between cytoskeletal stiffness, nuclear abnormalities, and senescent phenotypes remain largely unknown. Here, using muscle‐derived mesenchymal stromal/stem cells (MSCs) from the Zmpste24?/? (Z24?/?) mouse (a model for HGPS) and human HGPS fibroblasts, we investigated the mechanical mechanism of progerin‐induced cellular senescence, involving the role and interaction of mechanical sensors RhoA and Sun1/2 in regulating F‐actin cytoskeleton stiffness, nuclear blebbing, micronuclei formation, and the innate immune response. We observed that increased cytoskeletal stiffness and RhoA activation in progeria cells were directly coupled with increased nuclear blebbing, Sun2 expression, and micronuclei‐induced cGAS‐Sting activation, part of the innate immune response. Expression of constitutively active RhoA promoted, while the inhibition of RhoA/ROCK reduced cytoskeletal stiffness, Sun2 expression, the innate immune response, and cellular senescence. Silencing of Sun2 expression by siRNA also repressed RhoA activation, cytoskeletal stiffness and cellular senescence. Treatment of Zmpste24?/? mice with a RhoA inhibitor repressed cellular senescence and improved muscle regeneration. These results reveal novel mechanical roles and correlation of cytoskeletal/nuclear stiffness, RhoA, Sun2, and the innate immune response in promoting aging and cellular senescence in HGPS progeria. 相似文献
76.
ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα 下载免费PDF全文
Chien‐Yao Fu Wei‐Wen Kuo Tsung‐Jung Ho Su‐Ying Wen Ling‐Chun Lin Yan‐Shen Tseng Hui‐Chuan Hung Vijaya Padma Viswanadha Chih‐Yang Huang 《Cell biochemistry and function》2016,34(8):606-612
ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS‐dependent pathway and a mitochondria‐dependent pathway by subsequently inducing caspase‐3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα. 相似文献
77.
78.
Wen‐Yuan Lin F. Xavier Pi‐Sunyer Chiu‐Shong Liu Tsai‐Chung Li Chia‐Ing Li Chih‐Yang Huang Cheng‐Chieh Lin 《Obesity (Silver Spring, Md.)》2009,17(6):1247-1254
Betel nut chewing has been reported to increase the risk of cardiovascular disease and all‐cause mortality. The reason is unclear. In this study, we investigated the association between betel nut chewing and general obesity (BMI ≥25 kg/m2) and central obesity (waist circumference (WC) ≥90 cm). A total of 1,049 male subjects, aged ≥40 years, were recruited from Taichung city in Taiwan in 2004. The relationships between betel nut chewing and general and central obesity were studied by multiple linear and logistic regression analyses. The prevalence of current and former betel nut chewing was 7.0 and 10.5% in our male Taiwanese cohort. Current/former betel nut chewers had a higher prevalence of general and central obesity when compared with individuals who had never chewed betel nut. Adjusted for age, diabetes, hypertension, lipids, smoking, alcohol drinking, physical activity, income, and education level, the odds ratios (ORs; 95% confidence intervals) of general and central obesity among the lower consumption of betel nut chewers were 1.78 (1.07, 2.96) and 1.19 (0.70, 2.02), respectively, compared to 2.01 (1.18, 3.41) and 1.89 (1.10, 3.23), respectively, among higher consumption chewers compared to individuals who had never chewed betel nut. The increasing ORs of general and central obesity with higher betel nut consumption revealed dose–response effects. Using multiple linear regression analyses, after adjusting for potential confounders, betel nut consumption was statistically significantly associated with BMI and WC. In conclusion, betel nut chewing was independently associated with general and central obesity in Taiwanese men. Dose–response effects of the association between betel nut consumption and general obesity as well as central obesity were found. 相似文献
79.
80.