Biology subjects

Hao, Q.

Publications and source records attributed to Hao, Q..

23 records · Page 2Linked to original sources

bioRxiv2020

Dietary propionate induces intestinal oxidative stress via inhibition of SIRT3-mediated SOD2 depropionylation

Propionate is a commonly used preservative in various food and feedstuffs and has been regarded as a food additive without safety concerns. However, we observed that dietary propionate supplementation induced intestinal damage in the context of high fat diet (HFD) in zebrafish. The intestinal damage was attributable to oxidative stress owing to impaired antioxidant capacity, which was caused by compromised SOD2 activity in the intestine. Global lysine propionylation analysis of the intestinal samples showed that SOD2 was propionylated at K132, and further biochemical assays demonstrated that K132 propionylation suppressed SOD2 activity. In addition, SIRT3 could directly interact with SOD2 and played an important role in regulating SOD2 activity via modulating depropionylation, and the enhanced SOD2 propionylation in zebrafish fed high fat plus propionate diet was attributable to reduced SIRT3 expression. Finally, we reveal that intestinal oxidative stress resulting from SOD2 propionylation contributed to the compositional change of gut microbiota, which further deteriorated intestinal oxidative stress independent of SIRT3. Collectively, the results in this study reveal a link between protein propionylation and intestine health, and suggest potential risk of a widely used food preservative in HFD context.

cell biology↗

bioRxiv2020

p53 induces ARTS to promote mitochondrial apoptosis

Apoptosis Related protein in TGF-{beta} Signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-{beta}, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here, we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, {gamma}-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.

cancer biology↗

bioRxiv2020

Core Role of TRPC6 in Regulating Airway Re-modelling in Chronic Obstructive Pulmonary Disease

RationaleThe mechanistic role of canonical transient receptor potential 6 (TRPC6) channel in chronic obstructive pulmonary disease (COPD) is poorly understood. ObjectivesThe purpose of this study is to determine the role of TRPC6 channel in COPD and its underlying signaling mechanisms in human airway smooth muscle cells (HASMCs). Methods and Main ResultsThe present study examined the effects of TRPC6 channel on nicotine and cigarette induced HASMCs proliferation, migration and mouse airway remodeling models. mRNA and protein expression of TRPC6 were increased in cultured HASMCs incubated with nicotine using real-time PCR and western blot analysis. Nicotine treatment significantly increased TRPC6 transcriptional activity through NF-{kappa}B in HASMCs with Co-IP and electrophoretic mobility shift assays (EMSA). Nicotine treatment also increased ROS level in HASMCs, this increase was attenuated by Nox inhibitor apocynin. miR-135a/b-5p down-regulated mRNA and protein level of TRPC6 in HASMCs, while luciferase reporter assay showed that miR-135a/b-5p targeted at the 3-UTR of TRPC6 mRNA. microRNA-135a/b-5p (miR-135a/b-5p), with a negative correlation to TRPC6 expression, was low in airway smooth muscle of COPD patients. Cigarette-induced airway remodeling mice model also exhibited a large increase in smooth muscle cell proliferation and smooth muscle layer mass with immunohistochemistry assay, this well-characterized airway remodeling was eliminated by lentivirus of TRPC6 knockdown or miR-135a/b-5p overexpression. ConclusionsNicotine exposure results in increased HASMCs proliferation and migration through NF-{kappa}B signaling. Inhalation of cigarette causes airway smooth muscle layer re-modeling due to altered TRPC6 elicited Ca2+ influx, miR-135a/b-5p abolishes this change both in vitro and in vivo.

cell biology↗

bioRxiv2019

Sequence based mapping identifies AWNS1, a candidate transcription repressor underlying awn suppression at the B1 locus in wheat

Awns are stiff, hair-like structures that grow from the spikelets of wheat (Triticum aestivum L.) and other grasses. In wild wheat relatives, awns play a role in seed dispersal. Awn suppression in domesticated wheat, where awns are shortened or even eliminated entirely, is variably adaptive with both awned and awnless types under widespread cultivation. Although the B1 locus on the long arm of chromosome 5A is a major determinant of awn suppression, no underlying gene or mechanism of action has been identified. Using association mapping, we identified a SNP marker located on the distal end of 5AL (5A28417) predictive of awn status in a panel of 640 U.S. winter wheat breeding lines, indicating that B1 was the determinant of awn suppression in this germplasm. Analysis of historical data available for the panel determined 5A28417 was also significantly associated with grain test weight. Evaluation of spike morphology and kernel traits was undertaken in a 341 RIL population developed from a cross between awned soft winter wheat cultivar LA95135 and awnless cultivar SS-MPV57. Awn suppression in the population co-segregated with 5A28417 and was co-located with QTL for number of spikelets per spike, kernel weight and kernel length. Fine-mapping located B1 to a region containing only two predicted genes, including a C2H2 zinc finger transcription factor 219 bp from 5A28417 that we named AWNS-A1. Deletions encompassing both genes were present in awned mutants of the awnless cultivar Brundage. Polymorphisms in the AWNS-A1 coding region were not observed in diverse wheat germplasm. However, sequencing of wheat lines representing different marker haplotypes in the surrounding region identified a deletion 3 kb downstream of AWNS-A1. A marker for this deletion was highly predictive of awn suppression in a collection of diverse wheat accessions, and indicates that AWNS-A1 is likely the major determinant of awn suppression in global wheat germplasm. AWNS-A1 is more highly expressed in developing spikes of awnless individuals, suggesting a mechanism for awn suppression.

genetics↗

bioRxiv2018

Cold Shock Fail to Restrain Pre-formed Bacterial Biofilm

Environmental temperature fluctuation has great impact on the formation of bacterial biofilm, while little information is available for assessing the influence of sharp temperature shifts on the fate of pre-formed biofilm. In this study, experimental evidence is firstly explored on the response of Vibrio parahaemolyticus pre-formed biofilm under cold shock (4 {degrees}C and 10 {degrees}C). Surprisingly, biofilm biomass of V. parahaemolyticus significantly increased during the period of cold shock as revealed by crystal violet staining. Polysaccharides and proteins contents in extracellular polymeric substances were gradually enhanced after cold shocks and exhibited high consistency. RT-qPCR demonstrated the expression of flagella and virulence-related genes were up-regulated. Most of QS and T3SS genes were slightly up-regulated, and three T3SS genes (vcrD1, vcrD2{beta} and vopD1) were down-regulated. Furthermore, the biofilm structure of V parahaemolyticus have been analyzed by Confocal laser scanning microscopy (CLSM), which sharply changed under cold shocks. The correlation analysis further displayed the significant correlation (P < 0.01) among biofilm structure parameters, and weak correlation (P < 0.05) between biofilm related genes and biofilm structure parameters. In conclusion, our results novel discovered that V. parahaemolyticus biofilm related genes were actively expressed and biofilm biomass was continuously increased, biofilm structure was tremendously changed after cold shock. This study underscored the risk that biofilm cells had the ability to adapt to low temperature shift.\n\nIMPORTANCEBiofilms are widespread in natural environments, especially on the surface of food and medical biomaterials, which threaten human safety from persistent infections. Previous studies simply focused on biofilm formation of microorganisms under steady state, however, the actual environment frequently fluctuated. V. parahaemolyticus is a widely distributed foodborne pathogen, temperature play a great role in its survival. Researchers generally assume that cold environment can restrain biofilm formation and bacterial activity. This study explored the effects of V. parahaemolyticus biofilm upon a shift from 37 {degrees}C to 4 {degrees}C or 10 {degrees}C from two aspects. On the one hand, the changes of biofilm biomass and EPS contents, the expression of biofilm related genes directly described that pre-formed bacterial biofilm could not be controlled efficiently in cold environment. On the other hand, the CLSM images revealed biofilm morphological structure change, the correlation analysis showed inner relationship among biofilm structure parameters and biofilm related genes. These results suggested that cold shock fail to restrain pre-formed bacterial biofilm, therefore be a potential risk in nature environment.

microbiology↗