Myotubularin-Related Protein14 Prevents Neointima Formation and Vascular Smooth Muscle Cell Proliferation by Inhibiting Polo-Like Kinase1.

Background Restenosis is one of the main bottlenecks in restricting the further development of cardiovascular interventional therapy. New signaling molecules involved in the progress have continuously been discovered; however, the specific molecular mechanisms remain unclear. MTMR14 (myotubularin-related protein 14) is a novel phosphoinositide phosphatase that has a variety of biological functions and is involved in diverse biological processes. However, the role of MTMR14 in vascular biology remains unclear. Herein, we addressed the role of MTMR14 in neointima formation and vascular smooth muscle cell (VSMC) proliferation after vessel injury. Methods and Results Vessel injury models were established using SMC-specific conditional MTMR14-knockout and -transgenic mice. Neointima formation was assessed by histopathological methods, and VSMC proliferation and migration were assessed using fluorescence ubiquitination-based cell cycle indicator, transwell, and scratch wound assay. Neointima formation and the expression of MTMR14 was increased after injury. MTMR14 deficiency accelerated neointima formation and promoted VSMC proliferation after injury, whereas MTMR14 overexpression remarkably attenuated this process. Mechanistically, we demonstrated that MTMR14 suppressed the activation of PLK1 (polo-like kinase 1) by interacting with it, which further leads to the inhibition of the activation of MEK/ERK/AKT (mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase/protein kinase B), thereby inhibiting the proliferation of VSMC from the medial to the intima and thus preventing neointima formation. Conclusions MTMR14 prevents neointima formation and VSMC proliferation by inhibiting PLK1. Our findings reveal that MTMR14 serves as an inhibitor of VSMC proliferation and establish a link between MTMR14 and PLK1 in regulating VSMC proliferation. MTMR14 may become a novel potential therapeutic target in the treatment of restenosis.

Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt.

Cardiac hypertrophy (CH) is an independent risk factor for many cardiovascular diseases, and is one of the primary causes of morbidity and mortality in elderly people. Pathological CH involves excessive protein synthesis, increased cardiomyocyte size, and ultimately the development of heart failure. Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family, which is involved in apoptosis, aging, inflammation, and autophagy. However, its exact function in CH is still unclear. Herein, we investigated the roles of MTMR14 in CH. We show that MTMR14 expression was increased in hypertrophic mouse hearts. Mice deficient in heart MTMR14 exhibited an aggravated aortic-banding (AB)-induced CH phenotype. In contrast, MTMR14 overexpression prevented pressure overload-induced hypertrophy. At the molecular level, prevention of CH in the absence of MTMR14 involved elevations in Akt pathway components, which are key elements that regulate apoptosis and cell proliferation. These results demonstrate that MTMR14 is a new molecular target for the treatment of CH.

Starch-enhanced degradation of HMW PAHs by Fusarium sp. in an aged polluted soil from a coal mining area.

The present study used strain ZH-H2 (Fusarium sp.) isolated by our group as the PAH-degrading strain and 5-6-rings PAHs as degradation objects. The soil incubation experiment was carried out to investigate the starch-enhanced degradation effects of HMW PAHs by Fusarium sp. in an Aged Polluted Soil from a Coal Mining Area. The results showed that the removal rates of BaP, InP and BghiP increased with increasing inoculation rate of ZH-H2 in the unsterile aged polluted soil of coal mining area, with the exception of BbF degradation which increased in the H2 treatment and then decreased. Different addition dosage of starch apparently resulted in degradation of 4 PAHs in soil, with removal rates of 14.47% for BaP, 23.83% for DbA, 30.77% for BghiP and 31.00% for InP obtained with treatment D2, respectively higher than in treatment D1. So starch addition apparently enhanced the degradation of the 4 PAHs, especially InP and BghiP, by native microbes in the aged HMW PAH-polluted soil. By adding starch to these aged polluted soils with inoculated strain ZH-H2, HMW-PAHs degradation was further improved and addition of 0.5 g kg-1 starch to soils with 1.0 g kg-1 Fusarium ZH-H2 (D2 + H2) performed best to the 4 HMW-PAHs in all of these combination treatments by a factor of up to 3.09, depending on the PAH. We found that the highest polyphenol oxidase activities under D2 + H2 treatments are consistent with the results of removal rates of 4 PAHs. Our findings suggest that the combination of Fusarium sp. ZH-H2 and starch offers a suitable alternative for bioremediation of aged PAH-contaminated soil in coal mining areas, with a recommended inoculation size of 0.5 g Fusarium sp. ZH-H2 and addition of 0.5 g kg-1 starch per kg soil.

Effects of cadium, zinc and lead on soil enzyme activities.

Heavy metal (HM) is a major hazard to the soil-plant system. This study investigated the combined effects of cadium (Cd), zinc (Zn) and lead (Pb) on activities of four enzymes in soil, including calatase, urease, invertase and alkalin phosphatase. HM content in tops of canola and four enzymes activities in soil were analyzed at two months after the metal additions to the soil. Pb was not significantly inhibitory than the other heavy metals for the four enzyme activities and was shown to have a protective role on calatase activity in the combined presence of Cd, Zn and Pb; whereas Cd significantly inhibited the four enzyme activities, and Zn only inhibited urease and calatase activities. The inhibiting effect of Cd and Zn on urease and calatase activities can be intensified significantly by the additions of Zn and Cd. There was a negative synergistic inhibitory effect of Cd and Zn on the two enzymes in the presence of Cd, Zn and Pb. The urease activity was inhibited more by the HM combinations than by the metals alone and reduced approximately 20%-40% of urease activity. The intertase and alkaline phosphatase activities significantly decreased only with the increase of Cd concentration in the soil. It was shown that urease was much more sensitive to HM than the other enzymes. There was a obvious negative correlation between the ionic impulsion of HM in soil, the ionic impulsion of HM in canola plants tops and urease activity. It is concluded that the soil urease activity may be a sensitive tool for assessing additive toxic combination effect on soil biochemical parameters.