scholarly journals Mitochondria in Sepsis-Induced AKI

2019 ◽  
Vol 30 (7) ◽  
pp. 1151-1161 ◽  
Author(s):  
Jian Sun ◽  
Jingxiao Zhang ◽  
Jiakun Tian ◽  
Grazia Maria Virzì ◽  
Kumar Digvijay ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Potential Role ◽  
Regional Blood Flow ◽  
Flow Distribution ◽  
Endothelial Activation ◽  
Therapeutic Approaches ◽  
Potential Therapeutic Target ◽  
Human Sepsis ◽  
Effective Drugs

AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%–80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.

scholarly journals Intracellular and Extracellular Roles of Granzyme K

2021 ◽  
Vol 12 ◽  
Author(s):  
Annemieke C. Bouwman ◽  
Kim R. van Daalen ◽  
Sandra Crnko ◽  
Toine ten Broeke ◽  
Niels Bovenschen
Keyword(s):  
Immune System ◽  
Therapeutic Target ◽  
Serine Proteases ◽  
Bacterial Infections ◽  
Thermal Injury ◽  
Current Knowledge ◽  
Endothelial Activation ◽  
Potential Therapeutic Target ◽  
Cytotoxic Cells

Granzymes are a family of serine proteases stored in granules inside cytotoxic cells of the immune system. Granzyme K (GrK) has been only limitedly characterized and knowledge on its molecular functions is emerging. Traditionally GrK is described as a granule-secreted, pro-apoptotic serine protease. However, accumulating evidence is redefining the functions of GrK by the discovery of novel intracellular (e.g. cytotoxicity, inhibition of viral replication) and extracellular roles (e.g. endothelial activation and modulation of a pro-inflammatory immune cytokine response). Moreover, elevated GrK levels are associated with disease, including viral and bacterial infections, airway inflammation and thermal injury. This review aims to summarize and discuss the current knowledge of i) intracellular and extracellular GrK activity, ii) cytotoxic and non-cytotoxic GrK functioning, iii) the role of GrK in disease, and iv) GrK as a potential therapeutic target.

scholarly journals Obesity Induced Collateral Growth Impairment: Potential Role of Endothelial Activation and Leukocyte Mobilization/Recruitment

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Matthew Distasi ◽  
Gonzalo Campana ◽  
Miguel Ortiz ◽  
Carlos Labarrere ◽  
Steven Miller ◽  
...  
Keyword(s):  
Potential Role ◽  
Endothelial Activation ◽  
Growth Impairment ◽  
Leukocyte Mobilization ◽  
Collateral Growth

scholarly journals Insight into Salivary Gland Aquaporins

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1547 ◽  
Author(s):  
Claudia D’Agostino ◽  
Osama A. Elkashty ◽  
Clara Chivasso ◽  
Jason Perret ◽  
Simon D. Tran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Physiological Role ◽  
Main Role ◽  
Osmotic Gradient ◽  
Therapeutic Approaches ◽  
Potential Therapeutic Target ◽  
Transmembrane Channel ◽  
Saliva Secretion ◽  
Insight Into

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

Kallikrein-related peptidase 7 overexpression in melanoma cells modulates cell adhesion leading to a malignant phenotype

2018 ◽  
Vol 399 (9) ◽  
pp. 1099-1105 ◽  
Author(s):  
Meriem Haddada ◽  
Hend Draoui ◽  
Lydia Deschamps ◽  
Francine Walker ◽  
Tiphaine Delaunay ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Potential Role ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Integrin Expression ◽  
Spheroid Formation ◽  
Malignant Phenotype ◽  
Potential Therapeutic Target ◽  
Β3 Integrin

AbstractWe recently reported that human melanoma cells, but not benign melanocytes, aberrantly express kallikrein-related peptidase 7 (KLK7). Here, we show a KLK7 overexpression-mediated decrease of cell adhesion to extracellular matrix binding proteins, associated with downregulation of α5/β1/αv/β3 integrin expression. We also report an up-regulation of MCAM/CD146 and an increase in spheroid formation of these cells. Our results demonstrate that aberrant KLK7 expression leads to a switch to a more malignant phenotype suggesting a potential role of KLK7 in melanoma invasion. Thus, KLK7 may represent a biomarker for melanoma progression and may be a potential therapeutic target for melanoma.

Evidence that levels of malate dehydrogenase and fumarase are increased by cAMP in rat myotubes

1984 ◽  
Vol 247 (1) ◽  
pp. C33-C38 ◽  
Author(s):  
J. C. Lawrence ◽  
W. J. Salsgiver
Keyword(s):  
Energy Metabolism ◽  
Malate Dehydrogenase ◽  
Potential Role ◽  
Primary Cultures ◽  
Phosphodiesterase Inhibitors ◽  
Dibutyryl Camp ◽  
Rat Skeletal Muscle ◽  
Oxidative Energy Metabolism ◽  
Enzymes Of Energy Metabolism

We have investigated the potential role of adenosine 3',5'-cyclic monophosphate (cAMP) in controlling levels of enzymes of energy metabolism in primary cultures of rat skeletal muscle cells. Incubating myotubes with cholera toxin or forskolin (2 persistent activators of adenylate cyclase) significantly increased the levels of two enzymes of oxidative metabolism, fumarase and malate dehydrogenase. These enzymes were also increased (1.5- to 2.0-fold) by phosphodiesterase inhibitors (caffeine, theophylline, theobromine, 3-isobutyl-1-methylxanthine, papaverine, MJ 1988, Ro 20–1724, or SQ 20009) and the cAMP derivatives: 8-bromo-cAMP or dibutyryl cAMP. In contrast two enzymes of glycolytic metabolism, lactate dehydrogenase and pyruvate kinase, were not consistently affected by these agents. The results presented provide strong evidence that an increase in cAMP can lead to an increase in certain enzymes of oxidative energy metabolism.

scholarly journals Study Progression of Apelin/APJ Signaling and Apela in Different Types of Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Longfei Liu ◽  
Xiaoping Yi ◽  
Can Lu ◽  
Yong Wang ◽  
Qiao Xiao ◽  
...  
Keyword(s):  
Stress Response ◽  
Energy Metabolism ◽  
G Protein ◽  
Potential Role ◽  
Cardiovascular Regulation ◽  
Cancer Development ◽  
Endogenous Ligand ◽  
Different Types ◽  
G Protein Coupled

Apelin is an endogenous ligand that binds to the G protein-coupled receptor angiotensin-like-receptor 1 (APJ). Apelin and APJ are widely distributed in organs and tissues and are involved in multiple physiological and pathological processes including cardiovascular regulation, neuroendocrine stress response, energy metabolism, etc. Additionally, apelin/APJ axis was found to play an important role in cancer development and progression. Apela is a newly identified endogenous ligand for APJ. Several studies have revealed the potential role of Apela in cancers. In this article, we review the current studies focusing on the role of apelin/APJ signaling and Apela in different cancers. Potential mechanisms by which apelin/APJ and Apela mediate the regulation of cancer development and progression were also mentioned. The Apelin/APJ signaling and Apela may serve as potential therapeutic candidates for treatment of cancer.

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