Yue-Yang Zhang,Le-Yu Huang,Huiling Wang,Sixuan Meng,Fei Yang,Shi-Yu Liu
Carboxylesterase 2 (CES2), an extensively expressed serine esterase which widely distributed in various organs and tissues, exerts important roles in maintaining normal physiological function while abnormal expression of CES2 was correlated with many metabolic diseases and cancers. Thus, to develop efficient tool for detection of CES2 activity is of great importance in related clinical diagnosis and research of physiological function of CES2. To date, several enzyme-activated fluorescent probes were developed for CES2 sensing. Among which regulation of CES2 in diseases such as diabetics, colitis, cancers and liver injury could be visualized. However, even though CES2 displayed relatively high expression level in kidney, its regulation in pathological process of kidney injury was rarely studied, and thus related preliminary investigation is in urgent demand. Herein, by rational design and construction of an enzyme-activated fluorescent probe (named as DDXB ) with high catalytic efficacy, sensitivity and specificity toward CES2, down-regulation of CES2 activity in acetaminophen (APAP)-induced liver injury and dextran sulfate sodium (DSS)-induced colitis model was successfully visualized. Most importantly, aberrant up-regulation of CES2 in streptozotocin (STZ), renal ischemia reperfusion (IR) injury (RIRI) and cisplatin (CDDP)-induced kidney injury model was first revealed via DDXB- based fluorescence imaging and further confirmed by immunohistochemistry (IHC) staining. Thus, preliminary evidence for identifying CES2 as potential biomarker of kidney injury were first provided, and the newly developed probe could serve as an efficient tool for related diagnosis or further investigation of CES2 physiological function in more diseases.
Lucheng Chen,Jiaying Yu,Qi Liu,Jiaxing Han,Daoxiang Su,Zhifei Wang
Carboxylesterase 2 (CES2) plays critical roles in lipid metabolism and exogenous detoxification, yet current detection methods lack specificity in complex biological systems. To overcome this limitation, we developed CLC-CES2, a near-infrared fluorescent probe rationally designed based on CES2's substrate recognition mechanisms. This probe demonstrates exceptional performance with near-infrared emission (695 nm), a large Stokes shift (145 nm), and a low detection limit (0.021 μg/mL). Biological validation using live cell imaging and zebrafish models demonstrated successful detection of endogenous CES2 activity. These results establish CLC-CES2 as an efficient molecular tool for investigating CES2- associated physiological and pathological processes.
Qingfeng Xie,Zhuo Cao,Weiling You,Xiaoping Cai,Mei Shen,Zhangyong Yin,Yiwei Jiang,Xin Wang,Siyu Ye
New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.
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