Biology subjects

Tang, Y.-P.

Publications and source records attributed to Tang, Y.-P..

3 recordsLinked to original sources

bioRxiv2023

Geranylgeranyl pyrophosphate (GGPP) is associated with hepatic lipid accumulation and insulin resistance in MAO by prenylating Perilipin4

Metabolically Abnormal Obesity (MAO) is characterized by hepatic steatosis and type 2 diabetes (T2D), in contrast to Metabolically Healthy Obesity (MHO). In this study, we investigated the role of hepatic geranylgeranyl pyrophosphate (GGPP), a metabolite of the mevalonate (MVA) pathway, in regulating the differences in lipid metabolism between MAO and MHO. Our findings revealed that GGPP levels were significantly elevated in individuals with MAO, and deficiency of GGPP in the liver ameliorated the defects associated with MAO. Furthermore, we discovered that the prenylation of the lipid droplet-associated protein Perilipin 4 by GGPP enhances the formation of large lipid droplets, thereby exacerbating hepatic lipid accumulation and insulin resistance. Notably, the inhibitor DGBP, targeting the GGPP synthase Ggpps, effectively attenuated the traits of MAO, offering novel insights into the treatment of this condition.

pathology↗

bioRxiv2023

A cataract-causing Y204X mutation of CRYβB1 promotes C-terminal degradation and higher-order oligomerization

Crystallin (Cry) proteins are a class of main structural proteins of vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode for these Cry proteins is the common cause for congenital cataract. Despite extensive studies, the pathogenic and molecular mechanisms remain unclear. In this study, we identified a novel mutation in CRYBB1 from a congenital cataract family, and demonstrated that this mutation led to an earlier termination of protein translation, resulting in a 49-residue truncation at the CRY{beta}B1 C-terminus. This mutant is susceptible to proteolysis and allows us to determine a 1.2- [A] resolution crystal structure of CRY{beta}B1 without the entire C-terminal domain. In this crystal lattice, two N-terminal domain monomers form a dimer that structurally resembles a wild-type (WT) monomer, but with different surface characteristics. Biochemical analyses suggest that this mutant is significantly more liable to aggregate and degrade, when compared to WT CRY{beta}B1. All our results provide an insight into the mechanism regarding how a mutant Cry contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in the opacity of eye lens.

biochemistry↗

bioRxiv2020

LncRNA s Landscape in the patients of primary gout by Microarray Analysis

To determine the differential profiles of long non-coding RNAs (lncRNAs) in Peripheral blood mononuclear cells (PBMCs) among acute gout (AG) patients, intercritical gout (IG) patients and healthy control subjects, and to explore the specific biomarkers for acute gout diagnosis and treatment in future. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary AG (n=3), IG (n=3) and healthy subjects (n=3). For comparison Bioinformatics analyses were performed to predict the roles of abberrantly expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results in 32 AG, 32 IG patients and 32 healthy control subjects. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified in gout. The microarray analysis identified 3421 and 1739 differentially expressed lncRNAs, 2240 and 1027 differentially expressed mRNAs in AG and IG (fold change>1.5, P<0.05; respectively), respectively. qRT-PCR results of 9 dysregulated genes were consistent with the microarray data. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. The expression levels of TCONS_00004393 and ENST00000566457 were significantly increased in the AG group than those in the IG group or healthy subjects (P<0.01, respectively). Moreover, the areas under the ROC curve were 0.955 and 0.961 for TCONS_00004393 and ENST00000566457,respectively. Our results provide novel insight into the mechanisms of the primary gout, and reveal that TCONS_00004393 and ENST00000566457 might be as candidate diagnostic biomarkers and targets for the treatment of acute gout.

genetics↗