CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2013
·Vol. 29
·期 4
·730-734
·
IF 0.735
Zhang Lei,Zhang Shi-tao,Zhang Xiao-ping,Sun Jing,Wang Yong-sen,Liu Yue-long,Xue Miao-miao,Wang Zhi,Xing Shu,Ma Jun-feng,Li Wan-nan,Fu Xue-qi
The protein tyrosine phosphatases(PTPs) comprise a family of enzymes that specifically dephosphorylate tyrosyl residues. Among them, SHP-1 has been regarded as one of the best validated intracellular tyrosine phosphatases. Downregulation of SHP-1 has shown remarkable efficacy in improving insulin sensitivity in vivo in insulin signaling pathway. In this study, we found the role of Candesartan cilexetil targeting at SHP-1. The results indicate that Candesartan cilexetil was a competitive inhibitor to SHP-1(IC 50 =85.6 μmol/L and K
i =24 μmol/L). We also found that Candesartan cilexetil was more sensitive towards SHP-1 compared with other PTPs. Through the consequence of Western blotting, it showed that Candesartan cilexetil can strengthen the level of tyrosine phosphorylation of several key cellular proteins[such as insulin receptor(IR), insulin receptor substrate(IRS) and ERK]_in insulin signaling pathway in HepG 2 cells and improve the insulin sensitivity through inhibiting the protein phosphorylation of SHP-1. These findings showed that Candesartan cilexetil might be an important inhibitor of SHP-1 and had a great application potential in the treatment of diabetes through inhibiting the level of SHP-1 in insulin signaling pathway.
研究领域:
药理学
·
分子生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2022
·Vol. 477
·期 5
·1439-1451
·
IF 3.842
Li Jie,Chen Rongchang,Lu Yongzhen,Zeng Yuwei
This study investigated the regulatory effects of microRNA-1278 (miR-1278) on airway inflammation, airway reconstruction, and the proliferation and apoptosis of airway smooth muscle cells (ASMCs) induced by transforming growth factor β1 (TGF-β1). The results showed that miR-1278 was upregulated in the blood and lung tissues (LTs) of patients with asthma compared with that in healthy volunteers; miR-1278 expression was also upregulated in asthmatic mice, and miR-1278 inhibition improved the LTs of asthmatic mice. Moreover, miR-1278 inhibited inflammation in asthmatic mice and counteracted the effect of TGF-β1 of induced proliferation and reduced apoptosis in ASMCs. DLRA indicated that miR-1278 targeted the 3′-UTR of Src-homology 2-containing phosphatase 1 (SHP-1). Furthermore, miR-1278 promoted ASMC proliferation, in which TGF-β1 played an important role by regulating the SHP-1/STAT3 signaling pathway. In conclusion, this study showed that miR-1278 played a critical role in the processes of airway remodeling and reduction of apoptosis by targeting SHP-1.
研究领域:
呼吸医学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EMBO Molecular Medicine
·
2026
·Vol. 18
·期 5
·1990
·
IF 7.9
Yini Huang,Yan Ye,Xinmei Zhu,Dengpan Liang,Ruiqin Cui,Xiaopeng Yuan,Xitao Li,Quanming Zou,Haibo Li,Wei Huang
The limitations of existing drugs and the development of drug resistance make it urgent to develop new drugs against methicillin-resistant Staphylococcus aureus (MRSA). The re-development of the antibacterial activity of drugs that have already been proven safe for human use is an effective way. In this study, we discovered that the Src homology region 2 domain-containing phosphatase-1 (SHP-1) agonist SC-43, exhibits potent activity against Gram-positive bacteria, including MRSA. The mode of action studies revealed that SC-43 inhibits the key enzyme coproporphyrin ferrochelatase (CpfC) of the coproporphyrin-dependent (CPD) heme synthesis pathway and interferes with the bacterial porphyrin metabolism. The determination of the structure of CpfC derived from S. aureus (SA CpfC ) in this study allowed us to reveal the inhibitory effect of SC-43 at the molecular level. Animal experiments showed that SC-43 has the potential to become a new anti-MRSA drug. In conclusion, this study discovered a new anti-MRSA activity of a drug currently undergoing clinical trials and simultaneously verified the feasibility of developing new anti-Gram-positive bacteria drugs by inhibiting the CPD pathway. The limitations of existing drugs and the emergence of drug resistance make the development of new therapies against methicillin-resistant Staphylococcus aureus (MRSA) increasingly urgent. Here, we demonstrate that the Src homology region 2 domain-containing phosphatase-1 (SHP-1) agonist SC-43 exhibits antibacterial activity against MRSA. The limitations of existing drugs and the emergence of drug resistance make the development of new therapies against methicillin-resistant Staphylococcus aureus (MRSA) increasingly urgent. Here, we demonstrate that the Src homology region 2 domain-containing phosphatase-1 (SHP-1) agonist SC-43 exhibits antibacterial activity against MRSA.
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2021
·
IF 3.905
Decai Chi,Dong Wang,Minghui Zhang,Hui Ma,Fuhui Chen,Yajiao Sun
Lung cancer is the leading cause of cancer mortality worldwide. CLEC12B , a C-type lectin-like receptor, is low-expressed in lung cancer tissues. However, the function of CLEC12B in lung cancer and its underlying mechanism remain unclear. Here, an obvious down-regulation of CLEC12B was observed in lung cancer cells compared with the normal lung epithelial cells. CLEC12B over-expression suppressed cell viability and cell cycle entry in lung cancer, along with the reduction of PCNA and cyclin D1 expressions, while silencing CLEC12B possessed the opposite effects. Over-expression of CLEC12B promoted lung cancer cell apoptosis, accompanied by decreased Bcl-2 and increased Bax, cleaved caspase-3 and cleaved caspase-9. Moreover, CLEC12B decreased phosphorylation of PI3K-p85 and AKT proteins. By contrast, CLEC12B knockdown activated the PI3K/AKT pathway. In vivo , CLEC12B inhibited tumor growth in lung cancer, which can be reversed by CLEC12B inhibition. Co-IP and immunofluorescence assays confirmed the interaction between CLEC12B and SHP-1, and CLEC12B over-expression increased SHP-1 level. Furthermore, knocking down SHP-1 abrogated the above biological phenotypes caused by CLEC12B elevation. Taken together, our findings demonstrate that CLEC12B serves as a tumor-suppressing gene in lung cancer through positively regulating SHP-1 expression, which may be mediated by the PI3K/AKT signaling pathway .
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）