Editor's Pick:A diet rich in omega-3 fatty acids may lower prostate cancer genetic risk
A diet rich in omega-3 polyunsaturated fatty acids found in certain fish or fish oil, nuts, seeds, and vegetable oils may help lower prostate cancer risk in individuals with a genetic predisposition to cancer. So conclude researchers from Wake Forest University School of Medicine in their study appearing online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation.
While many genetic mutations are known to predispose to cancer, it has remained unclear whether dietary fat can modulate the risk of developing cancer in genetically predisposed individuals. Some studies suggest that a diet rich in omega-3 polyunsaturated fatty acids reduces cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic predisposition to cancer, Yong Chen and colleagues studied Pten-knockout mice (which are predisposed to develop prostate tumors) and the effects on these mice of diets with defined levels of specific polyunsaturated fatty acids. The authors found that a nutritionally balanced diet high in omega-3 fatty acid reduced prostate tumor growth and increased survival in these animals, whereas omega-6 fatty acids had the opposite effects. Furthermore, introduction into the Pten-knockout mice of the enzyme omega-3 desaturase, which converts omega-6 to omega-3, reduced tumor growth in a manner similar to the omega-3 rich diet. The researchers went on to show that the effect of polyunsaturated fatty acids on prostate cancer development is mediated in part through cell death that is dependent on a protein known as Bad. Together, the data highlight the importance of the interaction between genes and diet in prostate cancer and imply a beneficial effect of omega-3 polyunsaturated fatty acids on delaying the onset of human prostate cancer. It will be interesting in future studies to determine if any beneficial effects can also be achieved by supplementing the diet with omega-3 polyunsaturated fatty acids after tumor initiation has occurred.
Title: Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids
Author Contact:
Yong Q. Chen
Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Phone: (336) 713-7655; Fax (336) 713-7660; E-mail: yqchen@wfubmc.edu
Karen Richardson
Senior Media Relations Manager
Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA.
Phone: (336) 716-4453; Fax: (336) 716-6841: Email: krchrdsn@wfubmc.edu
View the PDF of this article at: http://www.the-jci.org/article.php?id=31494
Cardiology:
Mending a broken heart: How to boost the number and function of cardiac stem cells
A current hope is that cardiac stem cells could one day be manipulated to rebuild cardiac tissue damaged by heart disease. In a study appearing online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation, Edward Morrisey and colleagues from the University of Pennsylvania address a fundamental question in the cardiac stem cell field what are the molecular pathways required for expansion and development of cardiac stem cells"
The authors have delineated a novel and essential pathway for the expansion of recently identified islet (Isl-1)positive cardiac progenitor cells. These cells help form the right ventricle and outflow tract of the developing heart. The authors show that Wnt signaling through activation of fibroblast growth factor 10 (FGF10) expression was required for expansion of Isl-1 cardiac progenitors in the anterior heart; loss of Wnt signaling lead to a loss of the right ventricle and defective development of the outflow tract while sparing the left sided structures of the heart. Isl-1 positive precursor cells with active Wnt signaling were fated to become outflow tract and right ventricular muscle cells. Activation of Wnt signaling lead to increased numbers of Isl-1 positive progenitors, increased FGF10 expression, and increased outflow tract development. The direct relationship between Wnt and FGF10 signaling was demonstrated by the finding that FGF10 is a direct target of Wnt/beta-catenin signaling in cardiac development. These data identify a pathway by which the number and function of cardiac progenitor stem cells can be amplified, thus providing critical insight into the ability to harness these cells for future cardiac reparative therapies.
Title: Wnt/beta-catenin signaling promotes expansion of Isl-1 positive cardiac progenitor cells through regulation of FGF signaling
Author Contact:
Edward E. Morrisey
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-3010; Fax: (215) 573-2094; Email: emorrise@mail.med.upenn.edu
Marc Kaplan
Director of Communications
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: (215) 662-2560; E-mail: Marc.Kaplan@uphs.upenn.edu
View the PDF of this article at: http://www.the-jci.org/article.php?id=31731
Cardiology:
Autophagy plays a role in heart's poor response to stress
As a result of high blood pressure or cardiac injury the heart may compensate by increasing in size and mass a process known as hypertrophy. These changes may become irreversible after prolonged cardiac stress, resulting in diminished cardiac performance and possible heart failure. In a study appearing online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation, Joseph Hill and colleagues from the University of Texas Southwestern Medical Center examine the role of autophagy the tightly regulated recycling of cellular products leading to programmed cell death in heart failure. The authors found that pressure overload of the heart greatly increased cardiac autophagy and heart failure in mice. Furthermore, disruption of the gene encoding the protein Beclin1, a protein known to be required for autophagy, decreased cardiac muscle cell autophagy and diminished harmful structural changes to the heart under severe pressure stress. Conversely, Beclin 1 overexpression increased autophagy activity and the severity of harmful structural changes in the hearts of these animals. Taken together, the data implicate autophagy in the development of pressure/load-induced heart failure and as such it may be a target for novel therapeutic intervention.
Title: Cardiac autophagy is a maladaptive response to hemodynamic stress
Author Contact:
Joseph A. Hill
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Phone : (214) 648-1400; Fax: (214) 648-1450; E-mail: joseph.hill@utsouthwestern.edu
View the PDF of this article at: http://www.the-jci.org/article.php?id=27523
Ophthomology
All eyes are on the role of glutamate transporters in glaucoma
Glaucoma, a leading cause of irreversible blindness in the United States, usually occurs when increased fluid pressure in the eye damages the optic nerve. However, in a significant subset of glaucomas elevated intraocular pressure (IOP) is not a symptom [e.g. in normal tension glaucoma (NTG)] and in other cases a reduction in IOP does not prevent disease progression. In a study appearing online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation, Kohichi Tanaka and colleagues from Tokyo Medical and Dental University investigated IOP-independent mechanisms involved in the development of glaucoma. They show that mice deficient in the glutamate transporters GLAST or EAAC1 have spontaneous optical nerve degeneration without elevated IOP. In GLAST-deficient mice, administration of a glutamate receptor blocker prevented optical damage. These animals are believed to be the first animal models of NTG and offer a powerful system for further investigation of retinal degeneration in NTG and the development of therapies directed at preventing or treating IOP-independent glaucoma.
Title: The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma
Author Contact:
Kohichi Tanaka
Tokyo Medical and Dental University, Tokyo, Japan.
Phone : 81-3-5803-5846; Fax:81-3-5803-5843; E-mail: tanaka.aud@mri.tmd.ac.jp
View the PDF of this article at: http://www.the-jci.org/article.php?id=30178
Cardiology
New mouse model for the study of some forms of human hypertension
The angiotensin II receptor, type 1 (AT1) helps control blood pressure; its loss reduces blood pressure, while its overexpression leads to an increase in blood pressure. In a study appearing online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation, Eric Clauser and colleagues from Institute Cochin in Paris show that a mutation in AT1 that makes the receptor more sensitive to angiotensin II and the effects of its ligand longer lasting, causes a modest increase in blood pressure, as well as cardiac, vascular, and renal fibrosis, and cardiac dysfunction in mice. This new animal model reveals that constant activation of AT1 leads to cardiac and renal fibrosis in spite of only a modest increase in blood pressure, and will be useful for investigating the role of angiotensin II in organs affected by some forms of human hypertension.
Title: Gain-of-function mutant of angiotensin II receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice
Author Contact:
Eric Clauser
Institut Cochin, Paris, France
Phone : 33-153-73-27-50; Fax : 33-153-73-27-51; E-mail: clauser@cochin.inserm.fr
View the PDF of this article at: http://www.the-jci.org/article.php?id=28764
Physiology
Dietary phytochemicals regulate detoxification enzyme CYP1A1
Cytochrome P450 1A1 (CYP1A1) is a detoxification enzyme that plays an important role in the metabolism of dietary toxins and orally absorbed drugs. It can also produce highly carcinogenic metabolites from polycyclic aromatic hydrocarbons. In a study appearing online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation, Frank Gonzalez and colleagues from the National Cancer Institute report that dietary phytochemicals regulate whole-body CYP1A1 expression via an arylhydrocarbon nuclear translocator (Arnt) dependent system in the gut. The authors examined mice bred to lack Arnt expression in the intestinal epithelium and found that CYP1A1 expression and activity was markedly elevated in almost all non-gut tissues. Interestingly CYP1A1 expression was lost if the mice were fed a synthetic purified diet. However, CYP1A1 expression was restored following the addition of the natural phytochemical indole-3-carbinol to the diet of these mice. The data suggest that an Arnt-dependent pathway in the gut has an important role in the regulation of CYP1A1 expression and the metabolism of dietary-derived inducers of CYP1A1. This machinery may be involved in CYP1A1-mediated metabolism of dietary toxins and orally absorbed drugs.
Title: Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator dependent system in gut
Author Contact:
Frank J. Gonzalez
National Cancer Institute, Bethesda, Maryland, USA.
Phone: (301) 496-9067; Fax: (301) 496-8419; E-mail: fjgonz@helix.nih.gov
View the PDF of this article at: http://www.the-jci.org/article.php?id=31647
Journal
Journal of Clinical Investigation