Search results for " Mito"

Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

2018

Summary Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional respons…

IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition

2017

Abstract The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor–positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24− cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversio…

Oxidative stress preconditioning of mouse perivascular myogenic progenitors selects a subpopulation of cells with a distinct survival advantage in vi…

2018

AbstractCell engraftment, survival and integration during transplantation procedures represent the crux of cell-based therapies. Thus, there have been many studies focused on improving cell viability upon implantation. We used severe oxidative stress to select for a mouse mesoangioblast subpopulation in vitro and found that this subpopulation retained self-renewal and myogenic differentiation capacities while notably enhancing cell survival, proliferation and migration relative to unselected cells. Additionally, this subpopulation of cells presented different resistance and recovery properties upon oxidative stress treatment, demonstrating select advantages over parental mesoangioblasts in …

Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis

2016

Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppressed this production and induced cytotoxic effects in breast cancer stem-like cells, derived from dissociation of mammospheres. In particular, the drugs exerted a remarkable inhibitory effect on viability of stem-like cells. Such an effect was suppressed by N-acetylcysteine, suggesting a role of reactive oxygen species (ROS) generation in the cytotoxic effect. Instead z-VAD, a ge…

Editorial: Cell Stress, Metabolic Reprogramming, and Cancer

2018

Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis

2019

Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study aimed to investigate the contribution of oxidative stress to cancer-induced cachexia in the presence or in the absence of moderate exercise training. Mice bearing the colon C26 carcinoma, either sedentary or exercised, were used. The former showed muscle wasting and redox imbalance, with the activation of an antioxidant response and with upregulation of markers of proteasome-dependent…

Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells

2020

The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically,…

Polyphenols from Pennisetum glaucum grains induce MAP kinase phosphorylation and cell cycle arrest in human osteosarcoma cells

2019

Abstract Osteosarcoma is the most common bone tumor with a high prevalence among children and adolescents. Polyphenols are widely investigated for their chemopreventive and chemotherapeutic proprieties. In the present study, we explored the pro-apoptotic effects of pearl millet, Pennisetum glaucum, phenolic compounds (PGPC) on osteosarcoma U-2OS cells. Our results show that PGPC induced U-2OS cells death, in a dose dependent manner, with an IC50 of 80 μg/mL. Annexin-V and 7-AAD staining show that PGPC induced cell death mainly through caspase-dependent apoptosis as shown by a decrease in cell death when co-treated with pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketon…

MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming

2018

Summary Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metabolic switch are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes a robust bivalent energetics program early in cell reprogramming. Cells prone to undergo reprogramming exhibit high mitochondrial membrane potential and display a hybrid metabolism. We conclude that MYC proteins orchestrate a rewiring of somatic cell metabolism early in cell reprogramming, whereby somatic cells acquire the phenotypic plast…

The potential of aldehyde dehydrogenase 2 as a therapeutic target in cardiovascular disease.

2018

Mitochondrial aldehyde dehydrogenase (ALDH-2) plays a major role in the ethanol detoxification pathway by removing acetaldehyde. Therefore, ALDH-2 inhibitors such as disulfiram represent the first therapeutic targeting of ALDH-2 for alcoholism therapy. Areas covered: Recently, ALDH-2 was identified as an essential bioactivating enzyme of the anti-ischemic organic nitrate nitroglycerin, bringing ALDH-2 again into the focus of clinical interest. Mechanistic studies on the nitroglycerin bioactivation process revealed that during bioconversion of nitroglycerin and in the presence of reactive oxygen and nitrogen species the active site thiols of ALDH-2 are oxidized and the enzyme activity is los…