scholarly journals The Role of Peroxisome Proliferator-Activated Receptors in the Esophageal, Gastric, and Colorectal Cancer

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Fucci ◽  
Tommaso Colangelo ◽  
Carolina Votino ◽  
Massimo Pancione ◽  
Lina Sabatino ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Molecular Targets ◽  
Predictive Biomarkers ◽  
Cancer Development ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Peroxisome Proliferator Activated Receptors

Tumors of the gastrointestinal tract are among the most frequent human malignancies and account for approximately 30% of cancer-related deaths worldwide. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control diverse cellular functions such as proliferation, differentiation, and cell death. Owing to their involvement in so many processes, they play crucial roles also in the development and physiology of the gastrointestinal tract. Consistently, PPARs deregulation has been implicated in several pathophysiological conditions, including chronic inflammation and cancer development. This paper summarizes the current knowledge on the role that the various PPAR isoforms play in the pathogenesis of the esophageal, gastric, and intestinal cancer. Elucidation of the molecular mechanisms underlying PPARs' signaling pathways will provide insights into their possible use as predictive biomarkers in the initial stages of the process. In addition, this understanding will provide the basis for new molecular targets in cancer therapy and chemoprevention.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Anne Bugge ◽  
Susanne Mandrup
Keyword(s):  
Energy Homeostasis ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Special Focus ◽  
Peroxisome Proliferator ◽  
Subtype Specificity ◽  
Genome Wide ◽  
Peroxisome Proliferator Activated Receptors

The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPAR, /, and activate overlapping but also very different target gene programs. This review summarizes the insights into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1.

scholarly journals Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Ingrid Garajová ◽  
Tessa Y. Le Large ◽  
Adam E. Frampton ◽  
Christian Rolfo ◽  
Johannes Voortman ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Severe Disease ◽  
Predictive Biomarkers ◽  
Incidence Rates ◽  
Ductal Adenocarcinoma ◽  
Specific Expression ◽  
Response To Chemotherapy ◽  
Tumor Types

Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

scholarly journals Pathophysiological Role of K2P Channels in Human Diseases

2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Ion Homeostasis ◽  
Human Diseases ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
K2p Channels ◽  
And Function

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

scholarly journals Importance of the alternative NF-κB activation pathway in inflammation-associated gastrointestinal carcinogenesis

2016 ◽  
Vol 310 (11) ◽  
pp. G1081-G1090 ◽  
Author(s):  
Yvette J. Merga ◽  
Adrian O'Hara ◽  
Michael D. Burkitt ◽  
Carrie A. Duckworth ◽  
Christopher S. Probert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Signaling Pathway ◽  
Current Knowledge ◽  
Common Factor ◽  
Cancer Development ◽  
Gastrointestinal Malignancies ◽  
Activation Pathway ◽  
Inflammatory Bowel

Chronic inflammation is a common factor in the development of many gastrointestinal malignancies. Examples include inflammatory bowel disease predisposing to colorectal cancer, Barrett's esophagus as a precursor of esophageal adenocarcinoma, and Helicobacter pylori-induced gastric cancer. The classical activation pathway of NF-κB signaling has been identified as regulating several sporadic and inflammation-associated gastrointestinal tract malignancies. Emerging evidence suggests that the alternative NF-κB signaling pathway also exerts a distinct influence on these processes. This review brings together current knowledge of the role of the alternative NF-κB signaling pathway in the gastrointestinal tract, with a particular emphasis on inflammation-associated cancer development.

scholarly journals PPARs, Obesity, and Inflammation

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Rinke Stienstra ◽  
Caroline Duval ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Vascular Wall ◽  
Peroxisome Proliferator ◽  
Proinflammatory Mediators ◽  
Inflammatory Status ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors

The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.

scholarly journals Gastrointestinal Cytoprotection by PPAR Ligands

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Yuji Naito ◽  
Tomohisa Takagi ◽  
Toshikazu Yoshikawa
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Gastrointestinal Tract ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
Potential Therapeutic Target ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gastrointestinal Inflammation ◽  
Ppar Ligands

Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor that is known to play a central role in lipid metabolism and insulin sensitivity as well as inflammation and cell proliferation. According to the results obtained from studies on several animal models of gastrointestinal inflammation, PPAR has been implicated in the regulation of the immune response, particularly inflammation control, and has gained importance as a potential therapeutic target in the management of gastrointestinal inflammation. In the present paper, we present the current knowledge on the role of PPAR ligands in the gastrointestinal tract.

scholarly journals Thyroid hormone receptors regulate adipogenesis and carcinogenesis via crosstalk signaling with peroxisome proliferator-activated receptors

2009 ◽  
Vol 44 (3) ◽  
pp. 143-154 ◽  
Author(s):  
Changxue Lu ◽  
Sheue-Yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Biological Impact ◽  
Hormone Response Elements ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily. They are ligand-dependent transcription factors that interact with their cognate hormone response elements in the promoters to regulate respective target gene expression to modulate cellular functions. While the transcription activity of each is regulated by their respective ligands, recent studies indicate that via multiple mechanisms PPARs and TRs crosstalk to affect diverse biological functions. Here, we review recent advances in the understanding of the molecular mechanisms and biological impact of crosstalk between these two important nuclear receptors, focusing on their roles in adipogenesis and carcinogenesis.

scholarly journals Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

2020 ◽  
Vol 21 (18) ◽  
pp. 6462
Author(s):  
Emanuele Monda ◽  
Giuseppe Palmiero ◽  
Marta Rubino ◽  
Federica Verrillo ◽  
Federica Amodio ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Molecular Targets ◽  
Diverse Group ◽  
Myocardial Diseases ◽  
Immune System Activation ◽  
System Activation ◽  
Sarcomeric Genes

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

scholarly journals The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease

2017 ◽  
Vol 67 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Xin Sun ◽  
Yan Zhang ◽  
Meilin Xie
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Peroxisome Proliferator Activated Receptors ◽  
Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD. Many drugs developed so far are targeted at PPARs. Thus, the aim of this paper is to summarize the roles of PPARs in the treatment of NAFLD.

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