Structure and function of the adapter protein Gab and its role in the development of tumor, inflammation and cardiovascular diseases / 生理学报

Gab proteins, Grb2 (growth factor receptor binding protein 2)-associated binder, are important scaffolding adapter proteins required by many signaling pathways. In mammals, the Gab proteins mainly consist of Gab1, Gab2 and Gab3, and are involved in the amplification and integration of signal transduction evoked by a variety of extracellular stimuli, including various growth factors and cytokines. They are known to play key roles in many biological processes through the two classical signal pathways, SHP2/RAS/ERK and PI3K/AKT. In this review, we provide an overview of the structure and function of the scaffolding adapter, Gab, with a special focus on its role in tumor, inflammation and cardiovascular diseases.

Assessment of mitochondrial toxicity induced by zidovudine and adefovir dipivoxil in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the mitochondrial toxicities induced by zidovudine (AZT) and adefovir dipivoxil (ADV) antiviral drugs using a rat model system.</p><p><b>METHODS</b>Twelve healthy Sprague-Dawley rats were randomly divided into three equal groups and treated by oral gavage with zidovudine (125 mg/kg/day), adefovir (40 mg/kg/day), or saline (equal volume) for 28 days. The rats' body weights were measured once a week, and blood was collected every two weeks for blood and biochemical tests. All animals were sacrificed at the end of treatment, and liver, kidney, skeletal muscle, and cardiac muscle were collected by necropsy. Mitochondria were isolated from the respective tissue samples, and the activities of respiratory chain complexes were measured. DNA was purified from each sample and the mitochondrial DNA (mtDNA) content was monitored by quantitative real time PCR. Mitochondrial morphology was analyzed under electron microscope.</p><p><b>RESULTS</b>No significant adverse effects, including body weight loss, abnormal blood or biochemistry, were observed in rats treated with AZT or ADV. The activities of mitochondrial cytochrome c oxidase in liver and cardiac muscle were slightly decreased in rats treated with AZT (liver: 9.44+/-3.09 vs. 17.8+/-12.38, P?=?0.21; cardiac muscle: 32.74+/-5.52 vs. 24.74+/-20.59, P?=?0.28; kidney: 4.42+/-1.53 vs. 14.45+/-13.75, P?=?0.18; skeletal muscle: 33.75+/-8.74 vs. 40.04+/-2.49, P?=?0.45). The mtDNA content was significantly decreased in cardiac muscle of AZT-treated rats (cardiac muscle: 0.15+/-0.13 vs. 0.32+/-0.42, P?=?0.85). The morphology of mitochondria in liver, kidney, skeletal muscle, and cardiac muscle was significantly altered in the AZT-treated rats and included disappearance of the outer membrane, severely damaged structure, and swollen or completely absent cristae. No obvious effects were noted in the ADV- or saline-treated rats.</p><p><b>CONCLUSION</b>Significant adverse effects related to mitochondrial toxicity were observed in rats treated with AZT. The slightly decreased mtDNA content in ADV-treated rats may suggest that this antiviral drug can also cause mitochondrial toxic effects.</p>