Tropomyosins (Tms) are a family of highly conserved actin-binding proteins that play critical roles in a variety of processes, most notably, in the regulation of muscle contraction and relaxation. It is well known that different Tm isoforms have distinct functions and that altered expression of Tm isoforms could lead to changes in cardiac structure and function. To precisely define Tm isoform expression in the human heart, towards a better understanding of their functional roles, we have employed top-down mass spectrometry for in-depth proteomic characterization of Tm isoforms. Using a minimal amount of human heart tissue from rejected donor organs, we confirmed the presence of multiple Tm isoforms including α-Tm, β-Tm and κ-Tm in the human heart, with α-Tm being the predominant isoform, followed by minor isoforms of β-Tm and κ-Tm. Interestingly, our data revealed regional variations of Tm isoforms and post-translational modifications in the human heart. Specifically, the expression level of κ-Tm was highest in the left atrium but nearly undetectable in the left ventricle. The phosphorylation level of α-Tm (pα-Tm) was significantly higher in the atria than it was in the ventricles. The sequences of all Tm isoforms were characterized and the sites of post-translational modifications were localized. Clearly, top-down mass spectrometry is an attractive method for comprehensive characterization of Tm isoforms and post-translational modifications since it can universally detect and quantify all types of protein modifications without a priori knowledge and without the need for specific antibodies. 相似文献
The occurrence and health risk of hexabromocyclododecane (HBCD), a brominated flame retardant with its three diastereoisomers, in drinking water sources in the lower Yangtze River in China was investigated. Its concentration ranged from 0.58 to 3.71 ng/L and averaged at 1.18 ng/L. Among the three diastereoisomers of α-, β- and γ-HBCD, γ-HBCD was the dominant one accounting for 44% (ranging 27–82%) to the total concentration. Source of HBCD in the contaminated site was discussed according to its spatial distribution and diastereoisomer profile. The margin of exposure (MOE) approach was applied to evaluate the health risk of HBCD through drinking water by estimated exposure and derived reference dose. The MOE was 17 for adults and 12 for children in the worst-case scenario, suggesting a trivial health concern.
Because of persistent organic pollution in aquatic environments, the widely used organochlorine pesticide endosulfan, which is a potential endocrine disruptor, is expected to pose a significant risk to aquatic organisms. In the present study, we explored the potential endocrine-disrupting risk of β-endosulfan by investigating its effect on the growth, reproduction, plasma vitellogenin, and organ histology of adult zebrafish. We found that, although β-endosulfan did not significantly affect the growth of zebrafish, it greatly decreased the hatching rate, even at a concentration as low as 10 ng/L. Interestingly, the decrease of the hatching rate was highly correlated with pathological alterations of the testes. Additionally, the values of the gonadosomatic index were significantly reduced in female zebrafish treated with 200 ng/L β-endosulfan, which was also closely associated with ovarian histological changes. More importantly, a significant increase in the level of vitellogenin was observed in all male fish treated with β-endosulfan. Based on these findings, we conclude that β-endosulfan severely affects the reproductive function of zebrafish and the synthesis of vitellogenin in the liver, and thus, β-endosulfan has a serious endocrine disruption function in zebrafish. 相似文献