Publications by authors named "Benjamin Hemmelgarn"

5 Publications

  • Page 1 of 1

ΔNp73 overexpression promotes resistance to apoptosis but does not cooperate with PML/RARA in the induction of an APL-leukemic phenotype.

Oncotarget 2017 Jan;8(5):8475-8483

Department of Internal Medicine, Medical School of Ribeirao Preto, Brazil.

Here, we evaluated whether the overexpression of transcriptionally inactive ΔNp73 cooperates with PML/RARA fusion protein in the induction of an APL-leukemic phenotype, as well as its role in vitro in proliferation, myeloid differentiation, and drug-induced apoptosis. Using lentiviral gene transfer, we showed in vitro that ΔNp73 overexpression resulted in increased proliferation in murine bone marrow (BM) cells from hCG-PML/RARA transgenic mice and their wild-type (WT) counterpart, with no accumulation of cells at G2/M or S phases; instead, ΔNp73-expressing cells had a lower rate of induced apoptosis. Next, we evaluated the effect of ΔNp73 on stem-cell self-renewal and myeloid differentiation. Primary BM cells lentivirally infected with human ΔNp73 were not immortalized in culture and did not present significant changes in the percentage of CD11b. Finally, we assessed the impact of ΔNp73 on leukemogenesis or its possible cooperation with PML/RARA fusion protein in the induction of an APL-leukemic phenotype. After 120 days of follow-up, all transplanted mice were clinically healthy and, no evidence of leukemia/myelodysplasia was apparent. Taken together, our data suggest that ΔNp73 had no leukemic transformation capacity by itself and apparently did not cooperate with the PML/RARA fusion protein to induce a leukemic phenotype in a murine BM transplantation model. In addition, the forced expression of ΔNp73 in murine BM progenitors did not alter the ATRA-induced differentiation rate in vitro or induce aberrant cell proliferation, but exerted an important role in cell survival, providing resistance to drug-induced apoptosis.
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http://dx.doi.org/10.18632/oncotarget.14295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352415PMC
January 2017

The Role of Oxidative Stress-Induced Epigenetic Alterations in Amyloid-β Production in Alzheimer's Disease.

Oxid Med Cell Longev 2015 12;2015:604658. Epub 2015 Oct 12.

Division of Sports Medicine, Department of Family Medicine, Sports Health & Performance Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

An increasing number of studies have proposed a strong correlation between reactive oxygen species (ROS)-induced oxidative stress (OS) and the pathogenesis of Alzheimer's disease (AD). With over five million people diagnosed in the United States alone, AD is the most common type of dementia worldwide. AD includes progressive neurodegeneration, followed by memory loss and reduced cognitive ability. Characterized by the formation of amyloid-beta (Aβ) plaques as a hallmark, the connection between ROS and AD is compelling. Analyzing the ROS response of essential proteins in the amyloidogenic pathway, such as amyloid-beta precursor protein (APP) and beta-secretase (BACE1), along with influential signaling programs of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun N-terminal kinase (JNK), has helped visualize the path between OS and Aβ overproduction. In this review, attention will be paid to significant advances in the area of OS, epigenetics, and their influence on Aβ plaque assembly. Additionally, we aim to discuss available treatment options for AD that include antioxidant supplements, Asian traditional medicines, metal-protein-attenuating compounds, and histone modifying inhibitors.
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http://dx.doi.org/10.1155/2015/604658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620382PMC
July 2016

Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.

Nat Cell Biol 2015 Aug 20;17(8):1036-48. Epub 2015 Jul 20.

1] Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA [2] Department of Molecular Genetics, College of Biological Sciences, The Ohio State University, Columbus, Ohio 43210, USA [3] Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.

Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells using a murine intestinal model. We show that Myc and E2f1-3 have little impact on normal G1-S transitions. Instead, they synergistically control an S-G2 transcriptional program required for normal cell divisions and maintaining crypt-villus integrity. Surprisingly, Rb deficiency results in the Myc-dependent accumulation of E2f3 protein and chromatin repositioning of both Myc and E2f3, leading to the 'super activation' of a G1-S transcriptional program, ectopic S phase entry and rampant cell proliferation. These findings reveal that Rb-deficient cells hijack and redeploy Myc and E2f3 from an S-G2 program essential for normal cell cycles to a G1-S program that re-engages ectopic cell cycles, exposing an unanticipated addiction of Rb-null cells on Myc.
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http://dx.doi.org/10.1038/ncb3210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526313PMC
August 2015

Heart failure with preserved ejection fraction: Defining the function of ROS and NO.

J Appl Physiol (1985) 2015 Oct 14;119(8):944-51. Epub 2015 May 14.

Division of Sports Medicine, Department of Family Medicine, Sports Health & Performance Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio.

The understanding of complex molecular mechanisms underlying heart failure (HF) is constantly under revision. Recent research has paid much attention to understanding the growing number of patients that exhibit HF symptoms yet have an ejection fraction similar to a normal phenotype. Termed heart failure with preserved ejection fraction (HFpEF), this novel hypothesis traces its roots to a proinflammatory state initiated in part by the existence of comorbidities that create a favorable environment for the production of reactive oxygen species (ROS). Triggering a cascade that involves reduced nitric oxide (NO) availability, elevated ROS levels in the coronary endothelium eventually contribute to hypertrophy and increased resting tension in cardiomyocytes. Improved understanding of the molecular pathways associated with HFpEF has led to studies that concentrate on reducing ROS production in the heart, boosting NO availability, and increasing exercise capacity for HFpEF patients. This review will explore the latest research into the role of ROS and NO in the progression of HFpEF, as well as discuss the encouraging results of numerous therapeutic studies.
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http://dx.doi.org/10.1152/japplphysiol.01149.2014DOI Listing
October 2015

Commentaries on Viewpoint: The ongoing need for good physiological investigation: Obstructive sleep apnea in HIV patients as a paradigm.

J Appl Physiol (1985) 2015 Jan;118(2):247-50

Radiologic Sciences and Respiratory Therapy Division School of Health and Rehabilitation Sciences The Ohio State University College of MedicineUniversity of North Texas Health Science Center and Cardiovascular Research Institute Fort Worth, TexasLab. Sistemas Neurales Facultad de Química y Biología Depto. Biología, Universidad de Santiago (USACH) Lab. Neurociencias Facultad de Medicina Depto. Neurología P. Universidad Católica de ChileDepartment of Physiology & Biophysics Federal University of Minas Gerais Belo Horizonte, BrazilNeuroscience Research Australia UNSW Australia Sydney, Australia St. Vincent's Hospital Applied Medical Research Center Sydney, AustraliaNeuroscience Research Australia UNSW Australia Sydney, AustraliaDepartment of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital Aachen, GermanyVU University Medical Center The NetherlandsDepartment of Computer Science University of A Coruña, SpainDepartment of Surgery Upstate Medical University Syracuse, New YorkDepartment of Biology SUNY Cortland Cortland, New York.

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http://dx.doi.org/10.1152/japplphysiol.00989.2014DOI Listing
January 2015