Noncanonical Role of Telomerase in Regulation of Microvascular Redox Environment With Implications for Coronary Artery Disease.

Telomerase reverse transcriptase (TERT) (catalytic subunit of telomerase) is linked to the development of coronary artery disease (CAD); however, whether the role of nuclear vs. mitchondrial actions of TERT is involved is not determined. Dominant-negative TERT splice variants contribute to decreased mitochondrial integrity and promote elevated reactive oxygen species production.

Autophagy, TERT, and mitochondrial dysfunction in hyperoxia.

Ventilation with gases containing enhanced fractions of oxygen is the cornerstone of therapy for patients with hypoxia and acute respiratory distress syndrome. Yet, hyperoxia treatment increases free reactive oxygen species (ROS)-induced lung injury, which is reported to disrupt autophagy/mitophagy. Altered extranuclear activity of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), plays a protective role in ROS injury and autophagy in the systemic and coronary endothelium.

Detrimental effects of chemotherapy on human coronary microvascular function.

Chemotherapy (CT) is a necessary treatment to prevent the growth and survival of cancer cells. However, CT has a well-established adverse impact on the cardiovascular (CV) system, even years after cessation of treatment. The effects of CT drugs on tumor vasculature have been the focus of much research, but little evidence exists showing the effects on the host microcirculation.

Myosin-IIA heavy chain phosphorylation on S1943 regulates tumor metastasis.

Nonmuscle myosin-IIA (NMHC-IIA) heavy chain phosphorylation has gained recognition as an important feature of myosin-II regulation. In previous work, we showed that phosphorylation on S1943 promotes myosin-IIA filament disassembly in vitro and enhances EGF-stimulated lamellipod extension of breast tumor cells. However, the contribution of NMHC-IIA S1943 phosphorylation to the modulation of invasive cellular behavior and metastasis has not been examined.

Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection-The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress.

Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (DNA) that can lead to oxidative stress-induced cardiovascular apoptosis.

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins.

Objective: We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia.

Approach And Results: Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot.

H1 linker histone promotes epigenetic silencing by regulating both DNA methylation and histone H3 methylation.

Epigenetic silencing in mammals involves DNA methylation and posttranslational modifications of core histones. Here we show that the H1 linker histone plays a key role in regulating both DNA methylation and histone H3 methylation at the H19 and Gtl2 loci in mouse ES cells. Some, but not all, murine H1 subtypes interact with DNA methyltransferases DNMT1 and DNMT3B.