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    Young Scientist Forum
  • Immune Checkpoint Molecules in Cancer Cells: Not in Their Places but on Their Duty
    YAN Xiao-Jun, WANG Dong-Lai
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 547-554. https://doi.org/10.13865/j.cnki.cjbmb.2022.04.0124
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    Immune checkpoints represent a group of inhibitory receptor molecules that are expresses in the surface of immune cells and play a pivotal role in maintaining immune homeostasis. In recent years, several key immune checkpoint molecules such as CTLA-4 and PD-1, has been found to exist in some kinds of tumor cells. These ectopic expressed checkpoint molecules are named as “cancer cell-intrinsic immune checkpoint molecules”. Although our understanding on cancer cell-intrinsic immune checkpoint molecules is quite limited, emerging evidence suggests that the expression and the biological functions of such molecules in different types of cancer cells are heterozygous and diverse. In particular, the discovery of “adaptive immune-independent” regulation on cancer cell behaviors would potentially benefit to design a customized cancer immune therapy, as well as to develop new therapeutic strategies for cancer. In this review, we will briefly describe the timeline of the studies, deeply discuss the complicated biological functions and the regulatory mechanisms (CTLA-4 and PD-1 as representative examples). And finally we put forward a research perspective on cancer cell-intrinsic immune checkpoint molecules. This review aims to present and promote the studies of cancer cell-intrinsic immune checkpoint molecules to the broad scientific community.
    • Reviews
  • Effect of Diabetes-Mediated Pericyte Injury on Blood-Spinal Cord Barrier Destruction after Spinal Cord Injury
    CAI Shu-Fang, XU Jing-Yu, WU Yan-Qing
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 555-562. https://doi.org/10.13865/j.cnki.cjbmb.2021.07.1198
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  • Exercise Enhances SIRT1 Expression and Improves Alzheimer's Disease
    CHEN Ke, ZHANG Xiang-Liang, DU Li-Tao
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 563-569. https://doi.org/10.13865/j.cnki.cjbmb.2021.07.1252
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    Alzheimer's disease (AD) is a neurodegenerative disease, β-amyloid (Aβ) deposition and Tau protein hyperphosphorylation are the main pathological features. Silent mating-type information regulation 2 homolog 1 (SIRT1) can deacetylate various types of histones and non-histones, and play an important role in the pathogenesis of AD. Recent studies found that exercise can activate SIRT1 to delay the progression of AD. The mechanisms may be as follows: inhibit the activity of β-secretase and increase the activity of α-secretase to reduce the production of Aβ; reduce the accumulation of hyperphosphorylated Tau protein; interact with PGC-1α to promote mitochondrial biogenesis; up-regulate PINK1/Parkin signaling pathway to improve mitochondrial autophagy; and deacetylate NF-κB to inhibit neuroinflammation. In addition, the protein levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in hippocampus are increased, and ApoE4 gene is inhibited to enhance synaptic plasticity. This article summarizes the role and mechanisms of exercise in improving AD by regulating SIRT1, and provides new ideas for the prevention and treatment of AD.
  • Regulation Mechanisms of Sirt7 in Pathophysiological Activities
    LU Yang-Yang, LI Yan, LUO Cheng
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 570-576. https://doi.org/10.13865/j.cnki.cjbmb.2021.06.1197
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    Silent mating type information regulator 2-related enzymes or sirtuin family proteins are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases. Sirt7 is a member of sirtuin family and locates in the nucleolus. In recent years, increasing studies have been conducted on Sirt7 and its functions are gradually elucidated. Besides the classic deacetylase activity, Sirt7 also possesses activities such as adenosine diphosphate (ADP)-ribosyltransferase, desuccinylase and deglutarylase. The active substrates of Sirt7 include histones, DNA damage repair related factors, small nucleolar ribonucleoprotein components (nucleolar fibrin, U3), transcription factors (GA binding protein β1 (GABPβ1), forkhead box protein O4, GATA4), cyclin dependent kinase 9, histone acetyltransferase 1, polymerase associated factor 53 (PAF53), Ras-related nuclear protein (Ran), nuclear factor of activated T cells 1, and p53, etc. Sirt7 could also regulate the functions of damage-specific DNA binding protein 1 (DDB1)/cullin 4/DDB1-cullin 4 related factors 1, Suv39h1/Sirt1, Myc, nuclear respiration factor 1 and Elk4, while the mechanisms involved are still unclear. These studies imply that Sirt7 plays important roles in genome integrity, RNA transcription regulation, stress resistance, metabolic adjustment, inflammation modulation and other pathophysiological activities. This review will sort out the mechanisms of Sirt7 in regulating the activities mentioned above. The regulation of Sirt7 expression and activity by adenylate activated protein kinase (AMPK), protein arginine methyltransferase 6 and ubiquitin specific peptidase 7 are also introduced. Finally, the problems in present researchof Sirt7 are discussed.
  • Biological Functions of CXCL12-CXCR4 in Human Malignant Tumors
    WANG Sen, LUO Ji-Xian, Istvan Boldogh
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 577-586. https://doi.org/10.13865/j.cnki.cjbmb.2021.06.1148
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    Metastasis and cell infiltration are the difficulties in the treatment of solid and lymphatic carcinoma and the main causes of disease recurrence and death. The migration of cancer cells is a prerequisite for tumor metastasis and invasion. The CXCL12-CXCR4 pathway plays an important role in the pathogenesis of solid tumors and leukemia. The interaction between CXCL12 and its receptor CXCR4 can activate multiple signaling pathways and regulate different physiological and pathophysiological processes. Thus, blocking CXCL12-CXCR4 binding and/or downstream pathways has clinical benefits in treating a variety of diseases and cancers. Although some CXCL12 and CXCR4 antagonists have been identified and have shown encouraging results in terms of antitumor activity, these drugs have not been widely used in clinical patients due to their serious toxic and side effects. There is an urgent need to develop novel CXCL12-CXCR4 axis antagonists for the treatment of tumors. Herein, we review the recent research progress of CXCR4 pathway in solid tumors and leukemia, and discuss the therapeutic value and future research direction of CXCR4 pathways in solid tumors and leukemia.
  • The Role of Bile Acid Receptors in Non-alcoholic Fatty Liver Disease (NAFLD)
    TIAN Meng, YAN Jun, LI Xun
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 587-594. https://doi.org/10.13865/j.cnki.cjbmb.2021.07.1220
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    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease and its incidence is increasing year by year worldwide. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrosis, play an important role in its occurrence and development. However, the understanding of NAFLD is still very poor, and there is still a lack of effective drugs in clinical practice. Researchers are trying to explore the etiology of NAFLD and a new breakthrough in its treatment. Bile acid is one of the many metabolites synthesized in the liver. In addition to helping fat digestion and absorption, bile acid also acts as a signal molecule to activate the bile acid receptor, which is an important transcriptional regulatory factor and plays an important role in maintaining normal physiological metabolism of the body. More and more evidence shows that the function of the bile acid receptor is closely related to the occurrence of NAFLD, and the study of its related roles and functions can provide new insights and drug therapeutic targets for the treatment of NAFLD. Bile acid receptors include nuclear receptors, such as farnesoid X receptor (FXR), pregnane X receptor (PXR), etc., and cell surface receptors, such as transmembrane G protein-coupled receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2) and M3 muscarinic receptor. In this review, we summarize the research progress on the role of bile acid receptors in the pathogenesis of NAFLD by regulating bile acid homeostasis, lipid and glucose metabolism, energy metabolism, liver inflammation and fibrosis, and we further elaborated on the current status of bile acid receptor agonists in the treatment of NAFLD, in order to have a more comprehensive understanding of the pathogenesis of NAFLD and find a more effective way of treatment.
  • The Mechanisms of the Production of Different Isoforms of Nuclear Factor E2-related Factor 1 and Their Role in Diseases
    JIA Man, LV Jin-Jing, XIANG Yuan-Cai
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 595-602. https://doi.org/10.13865/j.cnki.cjbmb.2021.09.1204
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    During the normal process of biological growth and development, NF-E2-related factor 1 (Nrf1/Nfe2l1) plays a unique role in maintaining intracellular homeostasis and organ integrity. The deficiency of Nrf1 will lead to severe oxidative stress, genomic instability, and result in liver cancer, neurodegenerative disorder and other diseases. In recent years, it has been found that Nrf1 could yield different activated isoforms or even opposite activity isoforms in a variety of ways to perform distinct functions, and the distribution of these isoforms may play a vital role in the process of tumor development. Therefore, to gain a better understanding of the function of Nrf1 isoforms in cells and tissues, we first briefly introduced its discovery process, and demonstrated the multiple mechanisms of distinct isoform production including selective shear processing, internal selective translation initiation, and post-translation shear processing. More importantly, three different post-translational processing models, transmembrane dynamic processing, site-specific processing, ubiquitin-dependent processing, were expounded in detail. Furthermore, the biological function of different isoforms of Nrf1 and its role in diseases were also summarized in the last section. Collectively, we focus on the production mechanism of different isoforms of Nrf1 and their roles in diseases so as to lay a foundation for finding new strategies for tumor treatment.
    • Research Papers
  • NAT10 Promotes Cervical Cancer Cell Malignant Behavior via N4-acetylcytidine Modification of DDR1 mRNA
    ZHANG Xue, TANG Hua
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 603-613. https://doi.org/10.13865/j.cnki.cjbmb.2022.04.0044
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  • Siglec-15 Promotes the Proliferation and Migration of Colorectal Cancer Cells and Inhibits the Infiltration of CD4+ andCD8+ T Cells in Tumor Tissues
    CHENG Min-Rong, LIU Hang-Feng, GAO Shu-Hua, ZHENG Jin-Xiu, YANG Tao
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 621-629. https://doi.org/10.13865/j.cnki.cjbmb.2022.03.1632
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    Sialic acid binding immunoglobulin type lectin-15 (Siglec-15), one of the Siglec gene family members, is a new immunosuppressive molecule. Siglec-15 is highly expressed in a variety of human tumor cells and tumor-associated macrophages, but the biological function of Siglec-15 in colorectal cancer (CRC) and its effect on the tumor immune microenvironment remains poorly understood. This study aimed to investigate the effects of aberrant expression of Siglec-15 on the biological behaviors of CRC cells and the infiltration of CD4+ T and CD8+ T cells. Firstly, mRNA expression level of Siglec-15 was assessed in human CRC tissues from the TCGA database. IHC staining was performed to detect Siglec-15 expression in 52 cases of human CRC and paired adjacent tissues. We found that the expression level of Siglec-15 in CRC was significantly higher than that in adjacent tissues (P<0.01). CCK8 assay and wound healing assay showed that knocking down Siglec-15 could inhibit the proliferation (P<0.01) and migration (P<0.05) of SW480 cells. CD8+ T cells were isolated from mouse spleen with anti-CD8 magnetic beads, and co-cultured with mouse MC38 CRC cells. It was found that overexpression of Siglec-15 in MC38 cells could inhibit CD8+ T-cell-mediated killing of tumor cells and inhibit the secretion of IFN-γ and TNF-α (P<0.01). Subsequent in vivo experiments showed that overexpression of Siglec-15 promoted tumor growth in tumor-bearing mice (P<0.05). In addition, high level of Siglec-15 in CRC tissues is associated with decreasing infiltration of CD4+ T cells and CD8+ T cells in the tumor microenvironment after single sample gene set enrichment analysis and IHC analysis of mouse xenograft tumor tissues and human CRC tissues (P<0.05). In conclusion, Siglec-15 may contribute to the progression of colorectal cancer through promoting the proliferation and migration of CRC cells and hampering CD4+ T cells and CD8+ T cells infiltration into tumor microenvironment. This study provides some new experimental basis for exploring the immunosuppressive effect of Siglec-15 in CRC.
  • GABAAR Agonists Inhibit the Release of Inflammatory Factors Through the NF-κB Signaling Pathway
    CHEN Xi, REN Xiao-Xi, DENG Ye-Yun, LIU Kang-Rui, ZHANG Jian-Liang
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 630-637. https://doi.org/10.13865/j.cnki.cjbmb.2022.03.1669
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    Activation and inflammation of microglial correlate with progressive neuronal apoptosis in neurodegenerative disorders such as Parkinson's disease (PD). γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, has recently been shown to play an inhibitory role in the immune system, but the mechanism is unclear. In this study, the results showed that LPS promoted the release of inflammatory factors in a dose-dependent manner compared with the control group (P<0.01). Meanwhile, cell viability and cytotoxicity assays showed that the released inflammatory factors could induce the decline of SH-SY5Y cell viability. BV2 microglia cells were pretreated with GABA and Muscimol, a GABAA receptor agonist, then treated with lipopolysaccharide (LPS) to induce inflammation in our model. Compared with the LPS group, the enzyme linked immunosorbent assay (ELISA) showed that pretreatment with GABA and muscimol inhibited the expression of inflammatory cytokines in a dose-dependent manner (P<0.05). Cell viability and cytotoxicity test results also showed that pretreatment of GABA and GABAAR agonist muscimol saved the decline of SH-SY5Y cell viability caused by inflammatory factors (P<0.05). In addition, immunofluorescence analysis and dual luciferase results showed that muscimol could inhibit NF-κB inflammatory pathways (P<0.0001,P<0.01). In conclusion, our results indicated that GABA could inhibit neuroinflammation in BV2 microglia cells and affect the proliferation of SH-SY5Y cells by GABAAR- NF-κB pathway, which provides a scientific basis for further study on regulating GABA in anti-inflammation function and development of new therapeutics.
  • Analysis of the Key Metabolites and Genes Involving in Ornithine-Urea Cycle in Mytilus coruscus
    WANG Ying, FAN Xiao-Jun, LIU Fei, ZHANG Xiao-Lin, FAN Mei-Hua, YAN Xiao-Jun, LIAO Zhi
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 638-647. https://doi.org/10.13865/j.cnki.cjbmb.2022.03.1643
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    The ornithine-urea cycle (OUC) plays important roles in metabolism. However, there is a lack of study of OUC in shellfish. For filling this gap, the mussel Mytilus coruscus was selected, and the key genes together with the metabolites of OUC pathway were analyzed in the mantle and adductor muscle, respectively, using a real-time fluorescent quantitative PCR and an amino-acid analyzer. Moreover, the changes of the metabolite concentrations and the gene relative expression level of OUC were analyzed after arginine injection. The δ13C (13C/12C) of the mussel shell was calculated by an Isotope cube after injection of urea with 13C stable isotope labeling. The results showed that both of the mantle and the adductor muscle contain relative high concentration of urea, and arginine injection significantly up-regulated the urea concentration (P<0.01) and down-regulated the citrulline concentration (P<0.01). The other metabolites, such as ornithine, were observed with remaining stability. In addition, the arginine injection increased significantly the relative expression level of urease gene in both mantle and adductor muscle (P<0.01). However, the expression levels of other genes were different in two tissues, indicating that the ornithine-urea cycle pathway has complex and different regulatory processes in these two tissues. Moreover, injection of 13C labeled urea significantly increased the ratio of δ13C in the mussel shells (P <0.01), suggesting that urea may be involved in the biomineralization process of mussel. These studies provided clues for further understanding of the relationship between the OUC pathway and biomineralization of mussel, as well as exploring the molecular mechanism of the tolerance of Mytilus to seawater acidification.
  • The Capping Protein β-Subunit Mediates Fusicoccin-induced Stomatal Movement in Arabidopsis
    WANG Pan, LI Zhao, ZHAO Ge-Qing, WU Yue-Ran, DOU Li-Ru , YU Rong
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 648-657. https://doi.org/10.13865/j.cnki.cjbmb.2022.03.1411
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    Actin dynamics in guard cells play a critical role in stomatal movement. Remodeling of actin arrays is triggered by different biotic and abiotic stimuli, which requires precise control. However, the molecular mechanism underlying this process is not well understood. Here we investigated whether and how the capping protein (CP) regulates actin filaments during fusicoccin (FC) -induced stomatal opening. We found that both stomatal opening and F-actin rearrangement are sensitive in the Capping Protein β-subunit (CPB) cpb-3 mutants, which resulted in its hypersensitivity to drought stress. The leaves detached from cpb-3 had a higher water loss rate (63.45%) than from the wild type (48.99%), and the stomatal aperture of cpb-3 was about 20% greater than in the wild type. After 1 h of FC treatment, the proportion of cpb-3 guard cells with radial actin arrays increased to 65.5% dramatically, while only approximately 47.2% guard cells in WT exhibited transversely oriented actin filaments. Moreover, the record of transmembrane Ca2+ fluxes by the non-invasive micro-test technique (NMT) showed that FC-induced rapid Ca2+transport was more obvious in cpb-3 guard cells, with a mean efflux of 212.86 pmol cm-2s-1 compared with 68.76 pmol cm-2s-1 in the wild type. K+ influx occurred as the same pattern. Collectively, our data suggest that CPB plays an important role in FC-induced stomatal movement through the regulation of actin dynamics and ion flux (Ca2+, K+etc.).
  • G6PD Regulates Cyclin E1 and CDK2 to Promote Cell Proliferation and Its Prognostic Value in Clear Cell Renal Cell Carcinoma
    YANG Zhe, NI Yue-Li, WANG Shu-Jie, LIU Wen-Jing, ZHU Yu-Zhi, CHE Rong, DUAN You-Bin, KUANG Ying-Min, ZHU Yue-Chun, ZHANG Qiao
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 658-670. https://doi.org/10.13865/j.cnki.cjbmb.2022.03.1592
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    Clear cell renal cell carcinoma (ccRCC) has been proved to be a metabolic disease with high metastasis rate and poor prognosis. Effective molecular markers for diagnosis, treatment and prognosis are very important for this disease. Glucose 6-phosphatedehydrogenase (G6PD) was highly expressed in ccRCC and suggested a poor prognosis. The molecular mechanism of its promotion of ccRCC cell proliferation needs to be unraveled. The purpose of this study was to investigate the regulatory effect of G6PD on the expression of Cyclin E1 and CDK2, and to reveal the prognostic value of G6PD, Cyclin E1 and CDK2 in ccRCC patients. Our results demonstrated that decreasing G6PD could inhibit G1/S phase transformation and ccRCC cell proliferation. G6PD regulated the expression of G1/S phase transformation and proliferation related genes, including Cyclin D1, CDK4, CDK6, Cyclin E1 and CDK2. Through TCGA dataset mining, the results showed that compared with the normal control group, the mRNA levels of Cyclin D1, Cyclin E1 and CDK2 were significantly increased in ccRCC, but the expression of CDK6 was significantly decreased and no change of the expression of CDK4. G6PD was negatively correlated with Cyclin D1 (P<0.0001). There was no significant correlation between G6PD and CDK4 or CDK6 (P>0.05). G6PD and Cyclin E1 (P<0.0001), G6PD and CDK2 (P<0.05) were positively correlated. The results of immunohistochemical analysis demonstrated that Cyclin E1 and CDK2 protein expression levels were significantly increased in ccRCC tumor tissues compared with adjacent normal tissues. Kaplan-Meier and Cox regression analysis showed that high expression of Cyclin D1 rather suggested a better overall prognosis in ccRCC patients, and the expression levels of CDK4 and CDK6 were not significant in predicting the overall survival rate of ccRCC patients. However, high expression of Cyclin E1 and CDK2 indicated poor prognosis in ccRCC patients. Further cell model analyses indicated that decreased expression of Cyclin E1 and CDK2 could significantly reverse the ability of G6PD in promotion of ccRCC cell proliferation. Taken together, compared with the proliferation related factors, including Cyclin D1, CDK4 and CDK6, G6PD tends to upregulate the expression of Cyclin E1 and CDK2 and promotes ccRCC tumor proliferation. The abnormal high expression of these three factors is expected to be an independent survival predictor of poor prognosis in ccRCC patients.
  • The Small Molecule Drug BNTA Alleviates Osteoarthritis Caused by High Cholesterol by Upregulating Insig1
    WANG Jun-Yan, CAO Chen-Xi, HU Xiao-Qing, CHENG Jin, AO Ying-Fang
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 671-679. https://doi.org/10.13865/j.cnki.cjbmb.2022.04.1021
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    Osteoarthritis (OA) is a common degenerative disease of the motor system with a high morbidity and disability rate. The pathogenesis of OA is not clear at present. Previous studies believe that the pathogenesis of OA is mainly related to trauma factors, while recent studies have shown that metabolic factors, including abnormal cholesterol metabolism, are also closely related to OA. The treatment of OA is mainly symptomatic treatment at the early stage and surgical treatment at the late stage, and there is no specific drug. Previously, BNTA, a small molecule drug with cartilage protective effects, has been shown to have a good effect on OA caused by trauma, but its effect on OA caused by high cholesterol remains unclear. In order to explore the therapeutic effect of BNTA on OA caused by high cholesterol and its mechanism, the OA model of rats was constructed by adopting high cholesterol diets, and paraffin sections of knee joints were taken for histological evaluation. Lipid accumulation in chondrocytes of rats was assessed by oil red O staining. The expression of genes and proteins related to anabolism, catabolism and cholesterol metabolism in chondrocytes was assessed by RT-qPCR, immunofluorescence and immunohistochemistry. The results showed that BNTA could alleviate OA pathological manifestations and improve the OARSI (Osteoarthritis Research Society International) score in the OA model of high cholesterol rats. In rat chondrocytes, BNTA can promote the expression of anabolism-related genes col2, sox9 and acan, inhibit the expression of catabolism-related genes mmp13 and adamts5, and improve the lipid accumulation caused by high cholesterol in rat chondrocytes. BNTA can up-regulate Insig1 expression in rat chondrocytes and the OA model of high cholesterol rats. This study confirmed that high cholesterol can aggravate OA in vivo and in vitro, and can increase lipid accumulation in rat chondrocytes. Taken together, BNTA can alleviate OA phenotypes induced by high cholesterol and improve abnormal lipid accumulation in chondrocytes, possibly by inhibiting cholesterol biosynthesis in cells by upregulating Insig1, thereby alleviating abnormal lipid accumulation.
  • Baicalin Promotes the Apoptosis of Respiratory Inflammatory Cells in Asthmatic Mice through Bitter Taste Receptors
    GUO Xue-Dong, YI Hui-Lan
    Chinese Journal of Biochemistry and Molecular Biol. 2022, 38(5): 680-688. https://doi.org/10.13865/j.cnki.cjbmb.2022.03.1538
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    Asthma is a heterogeneous disease that affects three hundred million people worldwide. About half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (Tas2rs) are expressed in respiratory system, and Tas2rs might be used as new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. Based on this situation, we studied the effect of bitter compound baicalin (BA) on the apoptosis of inflammatory cells in the respiratory tract of asthmatic mice and its relationship with bitter signal transduction. Male BALB/c mice were selected as the tested animals randomly divided into control group (CK), asthma mouse model group stimulated by intraperitoneal injection and aerosol inhalation of ovalbumin(OVA) and intragastric administration of BA intervention OVA-induced asthma group (OVA+BA). The results showed that inflammatory cells infiltration, alveolar septum thickening and diminished alveolarspaces were observed in the OVA group after HE staining. The above symptoms were significantly alleviated in OVA+BA group. The total number of inflammatory cells and classified cell count in the bronchoalveolar lavage fluid of mice in OVA group were increased, and the number of inflammatory cells in BA intervention group were decreased significantly (P <0.05). Analysis of real-time quantitative PCR showed that the expression levels of mucin Muc5ac were significantly increased in the lung in OVA group (P <0.05), while the expression levels of Muc5ac in OVA+BA group were significantly lower than that in OVA group (P <0.05). The expression of Tas2r108, Tas2r126, Tas2r135, Tas2r143 and their downstream signal transduction molecules α-gust and Trpm5 were down-regulated in OVA group (P <0.05). In OVA group, the transcription of pro-apoptotic factors P53, Bax and Casp3 was inhibited,and decreased activity of caspase3 was detected, whereas the transcription of anti-apoptotic factor Bcl2 was up-regulated (P <0.05). In OVA+BA group, the transcription of tested Tas2rs genes and downstream signal transduction molecules (P <0.05), as well as pro-apoptotic genes P53, Bax and Casp3 were all up-regulated associated with the decreased Bcl2 expression and increased caspase3 activity (P<0.05). Our results suggest that BA might function as a bitter taste receptor agonist to mediate the regulation of respiratory tract inflammatory cells apoptosis by activating the bitter signal transduction system, and thus to reduce the lung inflammation and injury in asthmatic mice.
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