Journal of Cellular Signaling

Commentary Open Access

Targeting Lipid Metabolism for Better Management of Coronavirus SARS-COV-2 Infections: Intervention, Antiviral Drug Development, and Challenges

Yuting Wang, Peiran Chen, Ming-Liang He

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although has faded from public view, the virus itself remains highly active and continues to mutate, continuously causing infections. The population faces the risk of severe outcomes caused by virus infection (e.g., multi-organ tissue injury and acute respiratory distress syndrome (ARDS)). Furthermore, patients with chronic diseases (cardiovascular diseases, diabetes) are at risk of developing severe sequelae or even elevated mortality. 

Review Article Open Access

Navigating the Adipocyte Precursor Niche: Cell-Cell Interactions, Regulatory Mechanisms and Implications for Adipose Tissue Homeostasis

Devesh Kesharwani, Aaron Clifford Brown

Support for stem cell self-renewal and differentiation hinges upon the intricate microenvironment termed the stem cell 'niche'. Within the adipose tissue stem cell niche, diverse cell types, such as endothelial cells, immune cells, mural cells, and adipocytes, intricately regulate the function of adipocyte precursors. These interactions, whether direct or indirect, play a pivotal role in governing the balance between self-renewal and differentiation of adipocyte precursors into adipocytes. 

Commentary Open Access

Teaching an Old Drug a New Trick: Targeting Treatment Resistance in Genitourinary Cancers

Karina Aguilar, Anuj K. Sharma, Tianyu Yang, Dipen Mehta, Chandramukhi S. Panda, Vinata B. Lokeshwar

In the quest for improving the clinical outcome of patients with metastatic genitourinary cancers, including metastatic renal cell carcinoma (mRCC), the emphasis often is on finding new targeted therapies. However, two studies by Jordan et al. (Oncogenesis 2020) and Wang et al. (Cancer Cell Int 2022) demonstrate the feasibility of improving the efficacy of a modestly effective drug Sorafenib against mRCC by attacking a mechanism hijacked by RCC cells for inactivating Sorafenib.

Research Article Open Access

Phorbol-12-Myristate-13-Acetate (PMA) Reactivates Replication from HIV-1 Latency and Induces Jurkat Cell Death

Xue Wang, Jiangqin Zhao, Indira Hewlett

HIV-1 has the capability to establish latency during early infection in CD4+ cells, posing a significant challenge to the efforts aimed at curing HIV-1/AIDS. One extensively explored strategy to address this viral latency is the "shock-and-kill" approach. This involves reactivating viral replication using latency reversal agents (LRAs) to induce the death of infected cells. Regrettably, no LRAs with proven effectiveness have been identified thus far.

Research Article Open Access

MKP-2 Deficiency Leads to Lipolytic and Inflammatory Response to Fasting in Mice

Sadie Junkins, Gabrielle Westenberger, Jacob Sellers, Isabel Martinez, Nabin Ghimire, Cassandra Secunda, Morgan Welch, Urja Patel, Kisuk Min, Ahmed Lawan

The liver plays a crucial role in maintaining homeostasis for lipid and glucose. Hepatic lipid synthesis is regulated by nutritional signals in response to fasting and refeeding. It is known that overnutrition regulates MAPK-dependent pathways that control lipid metabolism in the liver by activating MAPK phosphatase-2 (MKP-2). Uncertainty still exists regarding the regulatory mechanisms and effects of MKP-2 on hepatic response to fasting.

Review Article Open Access

Optogenetics Sheds Light on Brown and Beige Adipocytes

Aaron Clifford Brown

Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders.

Research Article Open Access

Depleting Cellular Retinoic Acid Binding Protein 1 Impairs UPR^mt

Chin-Wen Wei, Thomas Lerdall, Fatimah Najjar, Li-Na Wei

Mitochondrial dysfunction underlines neurodegenerative diseases which are mostly characterized by progressive degeneration of neurons. We previously reported that Cellular retinoic acid Binding protein 1 (Crabp1) knockout (CKO) mice spontaneously developed age-dependent motor degeneration, with defects accumulated in spinal motor neurons (MNs), the only cell type in spinal cord that expresses CRABP1.

Original Research Open Access

Resveratrol and Astaxanthin Protect Primary Human Nasal Epithelial Cells Cultured at an Air-liquid Interface from an Acute Oxidant Exposure

Ayaho Yamamoto, Peter D. Sly, Nelufa Begum, Abrey J. Yeo, Emmanuelle Fantino

Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to the airway epithelium from OS. Resveratrol and astaxanthin are nutritional compounds that have shown diverse benefits including protection against OS and inflammation in various situations.

Research Article Open Access

Redox Homeostasis in Well-differentiated Primary Human Nasal Epithelial Cells

Ayaho Yamamoto, Peter D. Sly, Anna Henningham, Nelufa Begum, Abrey J. Yeo, Emmanuelle Fantino

Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions but can be disturbed by environmental exposures. The mechanism(s) underlying the induction and impact of OS on airway epithelium and how these influences on respiratory disease is poorly understood.

Commentary Open Access

Oxidative DNA Damage: A Role in Altering Neuronal Function

Adib Behrouzi, Mark R. Kelley, Jill C. Fehrenbacher

A role for oxidative stress in the etiology of myriad neuropathologies is well accepted. However, the specific effects of oxidative DNA damage in the onset or promotion of neuronal dysfunction have been less studied. In our recent publication by Behrouzi et al. (Oxidative DNA Damage and Cisplatin Neurotoxicity Is Exacerbated by Inhibition of OGG1 Glycosylase Activity and APE1 Endonuclease Activity in Sensory Neurons), inhibition of enzymes that play a role in repairing oxidative DNA damage exacerbated neurotoxic effects of the chemotherapeutic agent, cisplatin. 

Mini Review Open Access

MAGIs: Junctional Scaffolds Linking Inter-Cellular Junction Architecture, Actin Cytoskeleton Dynamics, and Signaling Pathways

Lisa Heron-Milhavet, Alexandre Djiane

MAGIs (membrane-associated guanylate-kinases (MAGUK) inverted) are apical scaffolds conserved across evolution, which regulate cellular junctions. Low expression of MAGIs has been associated with tumorigenesis in a wide variety of cancers. This “tumor-suppressive” function of MAGIs has stimulated many studies to better understand the processes they control, and how their misregulation could contribute to cancer progression.

Research Article Open Access

Expression and Localization of Phosphoinositide-Specific Phospholipases C in Cultured, Differentiating and Stimulated Human Osteoblasts

Sara Daisy Casoni, Alessia Romanelli, Marta Checchi, Serena Truocchio, Marzia Ferretti, Carla Palumbo, Vincenza Rita Lo Vasco

The osteoblasts contribute to bone homeostasis maintaining the bone mass, and intervene in bone injuries repair. Insights in the events leading to the proliferation and differentiation of osteoblasts might allow uncover potential molecular targets to control the complex mechanisms underlying bone remodeling. Signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to calcium-related signaling, including the Phosphoinositide (PI) pathway.

Review Article Open Access

Differentiation and Subtype Specification of Enteric Neurons: Current Knowledge of Transcription Factors, Signaling Molecules and Signaling Pathways Involved

Nastasia Popowycz, Leen Uyttebroek, Guy Hubens, Luc van Nassauw

The enteric nervous system is the largest component of the autonomic nervous system. It contains a broad network of interconnected plexuses and enteric neuronal subtypes which are in charge of the normal functioning of the gastrointestinal tract. Vagal and sacral neural crest cells are at the basis of the enteric nervous system development. These cells undergo multiple processes such as migration, proliferation and differentiation to finally form a functional enteric nervous system.

Commentary Open Access

The Outcome of Tumor Ablation Therapies is Determined by Stress Signaling Networks

Mladen Korbelik

Increasingly prominent roles in interventional oncology are held by various tumor ablation therapies performed by direct applications of local acute trauma-inducing insult to the targeted lesion aiming for its rapid in situ destruction. These therapies include treatments based on various forms of thermal energy delivery (photothermal, cryoablation, microwave ablation, radiofrequency ablation), non-thermal illumination (photodynamic therapy), electric field exposure, or high hydrostatic pressure

Research Article Open Access

Chronic IL-1 Exposed AR⁺ PCa Cell Lines Show Conserved Loss of IL-1 Sensitivity and Evolve Both Conserved and Unique Differential Gene Expression Profiles

Shayna E. Thomas-Jardin, Mohammed S. Kanchwala, Haley Dahl, Vivian Liu, Rohan Ahuja, Reshma Soundharrajan, Nicole Roos, Sydney Diep, Amrit Sandhu, Chao Xing, Nikki A. Delk

Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa androgen receptor (AR) expression concomitant with the upregulation of pro-survival proteins, causing de novo accumulation of castration-resistant PCa cells.

Review Article Open Access

Hydrogen Peroxide-induced Cell Death in Mammalian Cells

Tamutenda Chidawanyika, Surachai Supattapone

Hydrogen peroxide (H₂O₂) is an important intra- and extra-cellular signaling molecule that can determine cell fate. At low concentrations, H₂O₂ plays roles in proliferation, immunity, and metabolism. Cellular exposure to higher non-physiologic concentrations of H₂O₂ can result in oxidative stress.

Review Article Open Access

Function of Mitogen-Activated Protein Kinases in Hepatic Inflammation

Gabrielle Westenberger, Jacob Sellers, Savanie Fernando, Sadie Junkins, Sung Min Han, Kisuk Min, Ahmed Lawan

The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation.

Review Article Open Access

APE1/Ref-1 – One Target with Multiple Indications: Emerging Aspects and New Directions

Mahmut Mijiti, Rachel Caston, Silpa Gampala, Melissa L. Fishel, Jill C. Fehrenbacher, Mark R. Kelley

In the realm of DNA repair, base excision repair (BER) protein, APE1/Ref-1 (Apurinic/Apyrimidinic Endonuclease 1/Redox Effector - 1, also called APE1) has been studied for decades. However, over the past decade, APE1 has been established as a key player in reduction-oxidation (redox) signaling. In the review by Caston et al. (The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease), multiple roles of APE1 in cancer and other diseases are summarized. 

Commentary Open Access

APE1/Ref-1 as a Novel Target for Retinal Diseases

Curtis Heisel, Jonah Yousif, Mahmut Mijiti, Kostas Charizanis, Mitchel Brigell, Timothy W. Corson, Mark R. Kelley

APE1/Ref-1 (also called Ref-1) has been extensively studied for its role in DNA repair and reduction-oxidation (redox) signaling. The review titled: “The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease” by Caston et. al. summarizes the molecular functions of Ref-1 and the role it plays in a number of diseases, with a specific focus on various types of cancer.

Review Article Open Access

Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1

Anton M. Bennett, Ahmed Lawan

Obesity has reached a global epidemic and it predisposes to the development of insulin resistance, type 2 diabetes and related metabolic diseases. Current interventions against obesity and/or type 2 diabetes such as calorie restriction, exercise, genetic manipulations or established pharmacological treatments have not been successful for many patients with obesity and/or type 2 diabetes.

Research Article Open Access

Dendorbium Nobile Lindl. Alkaloids Suppress NF-κB and NLRP3 Signaling Pathways to Attenuate Lipopolysaccharide-induced Neuroinflammation

Jiaojiao Liu, Bo Liu, Xi He, Wu Qin, Jingshan Shi

The important immune cells in the brain are called microglia acting as the central junction between neuroinflammation and neurodegenerative diseases. In patients of cognitive disorders and Alzheimer’s disease (AD) animal models, amoebic morphology and inflammatory pathways are activated to release numerous cells in the inflammatory factors by active microglia.

Review Article Open Access

Is Citrate A Critical Signal in Immunity and Inflammation?

Alessia Zotta, Zbigniew Zaslona, Luke A. O’Neill

When immune cells are activated, they undergo metabolic change in order to have sufficient energy to function effectively. The Krebs cycle is one of the most important pathways involved in this response and citrate, a critical component of this pathway, regulates carbohydrate and lipid metabolism.

Commentary Open Access

Emerging Role of TRPML1 Mucolipin Endolysosomal Channel in Cancer

Giorgio Santoni, Matteo Santoni, Massimo Nabissi, Oliviero Marinelli, Consuelo Amantini, Maria Beatrice Morelli

The transient receptor potential mucolipin 1 (TRPML1) is an endolysosomal channel belonging to the TRP family. Clinically, mutations of TRPML1 have been responsible for a severe lysosomal storage disorder called mucolipidosis type IV.

Short Communication Open Access

Flow Cytometric Characterization of Accidental Cell Death Highlights Connections to Regulated Cell Death

Gary Warnes

Damage-Associated Molecular Patterns (DAMPs) are known by their nature to cause inflammatory responses in numerous disease states from cancer, trauma to age related diseases (e.g. atherosclerosis, Alzheimer’s and Parkinson’s diseases), these molecules are released by cells undergoing cell death.