Copper Metabolism and Diseases of Copper Metabolism
René Lontie in Copper Proteins and Copper Enzymes, 1984
Protein-synthesis inhibitor approaches to elucidating possible regulatory mechanisms are fraught with ambiguity; direct quantitative determinations of specific mRNA species are required for establishing transcription controls. Cousins and co-workers243,244 have begun such approaches with metallothionein. Poly(A)-mRNA was isolated from rat liver polysomes by oligo(dT)-cellulose chromatography.244 The isolated mRNA was translated in a cell-free wheat-germ system following the incorporation of [3H]amino acids. Newly synthesized metallothionein was quantitated after gel filtration or thiol-Sepharose chromatography. Most importantly, maximal polysomal metallothionein mRNA levels appeared to occur at approximately the same time (5 hr) as the maximal rate of hepatic metallothionein synthesis had in the earlier experiments described above. Thus, evidence for some effect of zinc on the regulation of metallothionein synthesis at the transcriptional level is more substantial than for any other protein related to copper metabolism. Finally, Durnam and Palmiter244a have been able to demonstrate an increased rate of metallothionein-mRNA synthesis with Cd, Zn, Cu, or Hg administration by current cDNA hybridization techniques. Possible postinductive effects of protein synthesis inhibitors on copper, cadmium, and zinc binding proteins have also been reported.245
Benzylpenicillin (Penicillin G)
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Pen G induces significant postantibiotic effect (PAE) in S. pyogenes in vitro and in vivo. This means there is a persisting suppression of bacterial growth after short exposure to Pen G (Odenholt et al., 1989; Odenholt et al., 1990; Winstanley, 1990). In serious infections such as necrotizing fasciitis, penicillin may be combined with a protein synthesis inhibitor such as clindamycin in an attempt to suppress toxin production (Stevens et al., 1988). This feature has also been demonstrated in invasive streptococcal disease (Carapetis et al., 2014).
An Overview of Microbes Pathogenic for Humans
Nancy Khardori in Bench to Bedside, 2018
Corynebacterium diphtheriae, the causative organism of diphtheria is the pathognomonic member of the Corynebacterium genus; they do not form spores. This bacteria produces a toxin that acts as a protein synthesis inhibitor. Patients often present with a gray pseudomembrane covering the posterior oropharynx, which can spread anywhere along the respiratory tree. Additionally, patients may develop myocarditis and neurologic symptoms. The widely available toxoid vaccine has led to significant decrease in this potentially fatal infection.
Stabilization of Nrf2 leading to HO-1 activation protects against zinc oxide nanoparticles-induced endothelial cell death
Published in Nanotoxicology, 2021
Longbin Zhang, Liyong Zou, Xuejun Jiang, Shuqun Cheng, Jun Zhang, Xia Qin, Zhexue Qin, Chengzhi Chen, Zhen Zou
We further explored the possible mechanisms for Nrf2 activation caused by ZnONPs. The mRNA expression of Nrf2 in HUVEC cells with or without ZnONPs treatment was determined. qPCR analysis results showed that ZnONPs treatment did not induce a significant change in the mRNA expression level of Nrf2 (Figure 6(A,B)), indicating that activation of Nrf2 did not occur at the transcriptional level. We then treated HUVEC cells with Z-Leu-Leu-Leu-al (MG-132), a potent proteasome inhibitor, prior to ZnONPs treatment. The western blot analysis results showed that MG132 dampened the ubiquitylation of Nrf2, indicating that the degradation of Nrf2 was dependent on the ubiquitin-proteasome pathway (Figure 6(C)). The protein synthesis inhibitor cycloheximide (CHX) was used to block protein synthesis to evaluate the degradation of protein. Under physiological conditions, Nrf2 is quickly degraded through the ubiquitin-proteasome pathway. However, we found that ZnONPs caused profound elevation of Nrf2 expression and slowed degradation of Nrf2 (approximately 9 h for the degradation of Nrf2 in the ZnONPs-treated HUVEC cells pretreated with CHX) (Figure 6(D)). Consistently, our results also illustrated that the total ubiquitination level was highly increased in response to ZnONPs treatment in a dose- and time-dependent manner (Figure 6(E,F)). Immunofluorescence analysis also demonstrated the elevation of ubiquitin in response to ZnONPs treatment (Figure 6(G)). Together, these results indicate that ZnONPs likely induce nonclassical activation of Nrf2 by dampening the degradation system.
Design, synthesis, and biological evaluation of 5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-Indole-2-Carbohydrazide derivatives: the methuosis inducer 12A as a Novel and selective anticancer agent
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Jun Wu, Hongyu Hu, Mingtao Ao, Zhenzhen Cui, Xiaoping Zhou, Jingbo Qin, Yafei Guo, Jingwei Chen, Yuhua Xue, Meijuan Fang
Methuosis is characterised by the accumulation of cytoplasmic vacuoles derived from macropinosomes. It has been reported that protein synthesis is needed during macropinosome formation. Bafilomycin A1 (Baf-A1), a selective inhibitor of vacuolar-type H + ATPase (V-ATPase), can inhibit nascent macropinosome formation and restore the vacuoles to normal morphology by inhibiting acid influx in cells24. Cycloheximide (CHX) is a protein synthesis inhibitor that can disrupt the process of macropinosome formation24. Accordingly, HeLa cells were treated with 12A or in combination with Baf-A1 or CHX for 8 h, and the morphological changes were then imaged. As shown in Figure 4(C), both CHX and Baf-A1 dramatically blocked the formation of vacuoles, indicating that 12A was a methuosis inducer.
GAS5, a FoxO1-actived long noncoding RNA, promotes propofol-induced oral squamous cell carcinoma apoptosis by regulating the miR-1297-GSK3β axis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Chengshun Gao, Chunmei Ren, Zhongxi Liu, Li Zhang, Ranran Tang, Xiaojie Li
Having identified that GAS5 promotes propofol-induced apoptosis via binding miR-1297, we next sought to investigate the downstream targets of miR-1297. Previous studies have indicated that propofol induces cell apoptosis by downregulating Bcl2 expression [19]. Thus, we asked whether the Bcl2 is also involved in propofol-induced OSCC cell apoptosis. To this end, we first detected the expression levels of Bcl2 family proteins Bcl2 and Mcl1 in response to propofol treatment. Interestingly, we found that Mcl1, but not Bcl2, was significantly decreased in UM-SCC6 cells upon propofol treatment. Additionally, phosphorylation of Mcl1 at ser 159 was increased in response to propofol treatment (Figure 4(A)). Increasing evidence has indicated that phosphorylation of Mcl1 at ser 159 plays an important role in Mcl1 stability [20,21]. To further validate that propofol affects Mcl1 protein stability, we treated the indicated cells with the protein synthesis inhibitor cycloheximide (CHX) together with or without propofol treatment. Notably, propofol decreased Mcl1 stability (Figure 4(B,C)).
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