A5086985617- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- MicroRNA in disease regulation
- Metabolism and Genetic Disorders
- Sarcoma Diagnosis and Treatment
- Extracellular vesicles in disease
- Birth, Development, and Health
- Histone Deacetylase Inhibitors Research
- Muscle Physiology and Disorders
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Cell death mechanisms and regulation
- Cardiac Ischemia and Reperfusion
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Tumors and Oncological Cases
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- 3D Printing in Biomedical Research
- Cancer-related gene regulation
- Eicosanoids and Hypertension Pharmacology
Children's Hospital Research Institute of Manitoba
2015-2025
University of Manitoba
2016-2025
Research Manitoba
2019-2024
University of Massachusetts Amherst
2020
Research Network (United States)
2020
Manitoba Health
2020
Manitoba Beekeepers' Association
2014-2019
York University
2000-2015
St. Boniface Hospital
2011
HeidelbergCement (Sweden)
2009
Abstract The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of intermediate metabolites geranylgeranylpyrophosphate (GGPP) farnesylpyrophosphate (FPP) used in prenylation proteins. Here we show that MEV inhibitor simvastatin induced significant cell death a wide range human tumor lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, breast cancer. Simvastatin apoptotic via intrinsic pathway. In all cancer types tested,...
Lipotoxicity is a form of cellular stress caused by the accumulation lipids resulting in mitochondrial dysfunction and insulin resistance muscle. Previously, we demonstrated that mitophagy receptor BNIP3L/Nix responsive to lipotoxicity accumulates response high-fat (HF) feeding. To provide better understanding this observation, undertook gene expression array shot-gun metabolomics studies soleus muscle from rodents on an HF diet. Interestingly, observed modest reduction several...
Mitochondrial transcription factor A (Tfam) is a nuclear-encoded gene product that imported into mitochondria and required for the of mitochondrial DNA (mtDNA). We hypothesized conditions known to produce biogenesis in skeletal muscle would be preceded by an increase Tfam expression. Therefore, rat was stimulated (10 Hz, 3 h/day). mRNA levels were significantly elevated (by 55%) at 4 days returned control 14 days. import intermyofibrillar (IMF) increased 52 61% (P < 0.05) 5 7 days,...
Activation of protein kinase A (PKA) by elevation the intracellular cyclic AMP (cAMP) level inhibits skeletal myogenesis. Previously, an indirect modulation myogenic regulatory factors (MRFs) was implicated as mechanism. Because myocyte enhancer factor 2 (MEF2) proteins are key regulators myogenesis and obligatory partners for MRFs, here we assessed whether these could be involved in PKA-mediated repression. Initially, silico analysis revealed several consensus PKA phosphoacceptor sites on...
Abstract Exposure to metabolic disease during fetal development alters cellular differentiation and perturbs homeostasis, but the underlying molecular regulators of this phenomenon in muscle cells are not completely understood. To address this, we undertook a computational approach identify cooperating partners myocyte enhancer factor-2 (MEF2) family transcription factors, known function. We demonstrate that MEF2 serum response factor (SRF) collaboratively regulate expression numerous...
Mitochondrial quality control is critical in muscle to ensure contractile and metabolic function. BNIP3L/Nix a BCL2 member, mitophagy receptor, has been implicated atrophy. Human genome-wide association studies (GWAS) suggest altered BNIP3L expression could predispose mitochondrial disease. To investigate function, we generated muscle-specific knockout model. bnip3l mice displayed ragged-red fiber phenotype, along with accumulation of mitochondria endo/sarcoplasmic reticulum morphology....
Vascular smooth muscle cells (VSMCs) maintain the ability to modulate their phenotype in response changing environmental stimuli. This modulation plays a critical role development of most vascular disease states. In these studies, stimulation cultured with platelet-derived growth factor resulted marked induction c-jun expression, which was attenuated by protein kinase Cdelta and calcium/calmodulin-dependent inhibition. Given that signaling pathways have been shown relieve repressive effects...
Rhabdomyosarcoma (RMS) is a muscle-derived tumor. In both pre-clinical and clinical studies Temozolomide (TMZ) has been recently tested against RMS; however, the precise mechanism of action TMZ in RMS remains unclear. Here we demonstrate that decreases cell viability RH30 C2C12 line, where cells display evidence mitochondrial outer membrane permeability. Interestingly, mouse myoblast line was relatively more resistant to TMZ-induced apoptosis. Moreover, observed activated biochemical...
Myocardin is a transcriptional co-activator required for cardiovascular development, but also promotes cardiomyocyte survival through an unclear molecular mechanism. Mitochondrial permeability transition implicated in necrosis, while pore closure mitochondrial maturation during cardiac development. We show that loss of myocardin function leads to subendocardial necrosis at E9.5, concurrent with elevated expression the death gene Nix. Mechanistically, we demonstrate knockdown reduces...
Alternative splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. Previously, we established hypoxia-inducible death factor Bnip3 as critical component of the intrinsic pathway.To investigate alternative pre-mRNA in postnatal ventricular myocytes during hypoxia.We identify novel previously unrecognized spliced variant (Bnip3Δex3) generated exon3 exclusively cardiac subjected to hypoxia. Sequencing Bnip3Δex3 revealed frame...
The antioxidant potential of carotenoids from aleurone, germ, and endosperm fractions barley, corn, wheat has been evaluated. HPLC analysis confirmed the presence lutein zeaxanthin (nd-15139 μg/kg) in extracts cereal grain fractions. properties using 2,2-diphenyl-1-picrylhydrazyl, oxygen radical absorbance capacity, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays revealed significantly higher (P<0.001) activity germ than aleurone Using...
The myocyte enhancer factor 2 (MEF2) transcription factors play important roles in neuronal, cardiac, and skeletal muscle tissues. MEF2 serves as a nuclear sensor, integrating signals from several signaling cascades through protein-protein interactions with kinases, chromatin remodeling factors, other transcriptional regulators. Here, we report novel interaction between the catalytic subunit of protein phosphatase 1alpha (PP1alpha) MEF2. Interaction occurs within nucleus, binding PP1alpha to...
Mitochondrial biogenesis is accompanied by an increased expression of components the protein import machinery, as well proteins destined for matrix. We evaluated role outer membrane receptor Tom20 varying its and measuring changes in malate dehydrogenase (MDH) differentiating C2C12 muscle cells. Cells transfected with had levels that were twofold higher than control Labeling cells followed immunoprecipitation MDH revealed equivalent increases import. This parallelism between rate was also...