scholarly journals Loss of Mitochondrial Control Impacts Renal Health

2020 ◽  
Vol 11 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Keizo Kanasaki ◽  
Julie E. Goodwin
Keyword(s):  
Metabolic Networks ◽  
Kidney Diseases ◽  
Therapeutic Agents ◽  
Kidney Cells ◽  
Loss Of Control ◽  
Cellular Processes ◽  
Mitochondrial Regulation ◽  
Cell Transdifferentiation ◽  
Mitochondrial Biosynthesis ◽  
Fuel Preference

Disruption of mitochondrial biosynthesis or dynamics, or loss of control over mitochondrial regulation leads to a significant alteration in fuel preference and metabolic shifts that potentially affect the health of kidney cells. Mitochondria regulate metabolic networks which affect multiple cellular processes. Indeed, mitochondria have established themselves as therapeutic targets in several diseases. The importance of mitochondria in regulating the pathogenesis of several diseases has been recognized, however, there is limited understanding of mitochondrial biology in the kidney. This review provides an overview of mitochondrial dysfunction in kidney diseases. We describe the importance of mitochondria and mitochondrial sirtuins in the regulation of renal metabolic shifts in diverse cells types, and review this loss of control leads to increased cell-to-cell transdifferentiation processes and myofibroblast-metabolic shifts, which affect the pathophysiology of several kidney diseases. In addition, we examine mitochondrial-targeted therapeutic agents that offer potential leads in combating kidney diseases.

scholarly journals Role of SIRT1 in HIV-associated kidney disease

2020 ◽  
Vol 319 (2) ◽  
pp. F335-F344 ◽  
Author(s):  
Xuan Wang ◽  
Ruijie Liu ◽  
Weijia Zhang ◽  
Deborah P. Hyink ◽  
Gokul C. Das ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Drug Targets ◽  
Cell Injury ◽  
Kidney Diseases ◽  
Sirtuin 1 ◽  
Kidney Cells ◽  
Sirt1 Expression ◽  
Hiv 1

Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.

Autophagy in Kidney Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 297-322 ◽  
Author(s):  
Mary E. Choi
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Therapeutic Benefit ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Kidney Diseases ◽  
Cellular Processes ◽  
Autophagy Pathway

Autophagy is a cellular homeostatic program for the turnover of cellular organelles and proteins, in which double-membraned vesicles (autophagosomes) sequester cytoplasmic cargos, which are subsequently delivered to the lysosome for degradation. Emerging evidence implicates autophagy as an important modulator of human disease. Macroautophagy and selective autophagy (e.g., mitophagy, aggrephagy) can influence cellular processes, including cell death, inflammation, and immune responses, and thereby exert both adaptive and maladaptive roles in disease pathogenesis. Autophagy has been implicated in acute kidney injury, which can arise in response to nephrotoxins, sepsis, and ischemia/reperfusion, and in chronic kidney diseases. The latter includes comorbidities of diabetes and recent evidence for chronic obstructive pulmonary disease–associated kidney injury. Roles of autophagy in polycystic kidney disease and kidney cancer have also been described. Targeting the autophagy pathway may have therapeutic benefit in the treatment of kidney disorders.

scholarly journals Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ai-Di Zhang ◽  
Shao-Xing Dai ◽  
Jing-Fei Huang
Keyword(s):  
Metabolic Network ◽  
Metabolic Networks ◽  
Kidney Diseases ◽  
Human Kidney ◽  
Specific Model ◽  
The Body ◽  
Data Production ◽  
Metabolic Basis ◽  
Metabolic Biomarkers

With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases.

scholarly journals NGAL and Metabolomics: The Single Biomarker to Reveal the Metabolome Alterations in Kidney Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
A. Noto ◽  
F. Cibecchini ◽  
V. Fanos ◽  
M. Mussap
Keyword(s):  
Structural Changes ◽  
Biomarker Discovery ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Functional Change ◽  
Therapeutic Interventions ◽  
Cellular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Cellular Processes ◽  
And Function

Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. Acute kidney injury (AKI) is one of a number of acute kidney diseases and consists of an abrupt decline in kidney function after an injury leading to functional and structural changes. The widespread availability of enabling technologies has accelerated the rate of novel biomarker discovery for kidney injury. The introduction of novel biomarkers in clinical practice will lead to better preventative and therapeutic interventions and to improve outcomes of critically ill patients. A number of biomarkers of functional change and cellular damage are under evaluation for early diagnosis, risk assessment, and prognosis of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the most promising biomarker of kidney injury; this protein can be measured by commercially available methods in whole blood, plasma, serum, and urine. Concomitantly, metabolomics appears to be a snapshot of the chemical fingerprints identifying specific cellular processes. In this paper, we describe the role of NGAL for managing AKI and the potential benefits deriving from the combined clinical use of urine NGAL and metabolomics in kidney disease.

scholarly journals Src family kinases in chronic kidney disease

2017 ◽  
Vol 313 (3) ◽  
pp. F721-F728 ◽  
Author(s):  
Jun Wang ◽  
Shougang Zhuang
Keyword(s):  
Kidney Disease ◽  
Tyrosine Kinases ◽  
Kidney Diseases ◽  
Src Family Kinases ◽  
Migration And Invasion ◽  
Tumor Treatment ◽  
Dominant Form ◽  
Cellular Processes ◽  
Immunodeficiency Virus ◽  
Autosomal Dominant Form

Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved.

scholarly journals Neddylation regulation of mitochondrial structure and functions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qiyin Zhou ◽  
Yawen Zheng ◽  
Yi Sun
Keyword(s):  
Structure And Function ◽  
Post Translational Modification ◽  
Exciting Field ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Mitochondrial Regulation ◽  
A Cell ◽  
And Function ◽  
Multiple Signaling ◽  
Ring E3 Ligases

AbstractMitochondria are the powerhouse of a cell. The structure and function of mitochondria are precisely regulated by multiple signaling pathways. Neddylation, a post-translational modification, plays a crucial role in various cellular processes including cellular metabolism via modulating the activity, function and subcellular localization of its substrates. Recently, accumulated data demonstrated that neddylation is involved in regulation of morphology, trafficking and function of mitochondria. Mechanistic elucidation of how mitochondria is modulated by neddylation would further our understanding of mitochondrial regulation to a new level. In this review, we first briefly introduce mitochondria, then neddylation cascade, and known protein substrates subjected to neddylation modification. Next, we summarize current available data of how neddylation enzymes, its substrates (including cullins/Cullin-RING E3 ligases and non-cullins) and its inhibitor MLN4924 regulate the structure and function of mitochondria. Finally, we propose the future perspectives on this emerging and exciting field of mitochondrial research.

scholarly journals The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9640
Author(s):  
Jing Chen ◽  
Chao Ye ◽  
Chao Wan ◽  
Gang Li ◽  
Lianci Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Infectious Diseases ◽  
Protein Kinases ◽  
Therapeutic Agents ◽  
Inflammasome Activation ◽  
Mitogen Activated Protein Kinases ◽  
Jnk Signaling ◽  
Cellular Processes ◽  
Prevention And Treatment ◽  
Mitogen Activated Protein

c-Jun N-terminal kinases (JNKs) are among the most crucial mitogen-activated protein kinases (MAPKs) and regulate various cellular processes, including cell proliferation, apoptosis, autophagy, and inflammation. Microbes heavily rely on cellular signaling pathways for their effective replication; hence, JNKs may play important roles in infectious diseases. In this review, we describe the basic signaling properties of MAPKs and JNKs in apoptosis, autophagy, and inflammasome activation. Furthermore, we discuss the roles of JNKs in various infectious diseases induced by viruses, bacteria, fungi, and parasites, as well as their potential to serve as targets for the development of therapeutic agents for infectious diseases. We expect this review to expand our understanding of the JNK signaling pathway’s role in infectious diseases and provide important clues for the prevention and treatment of infectious diseases.

scholarly journals Targeted Drug Delivery Systems for Kidney Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaohan Huang ◽  
Yanhong Ma ◽  
Yangyang Li ◽  
Fei Han ◽  
Weiqiang Lin
Keyword(s):  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Treatment Effectiveness ◽  
Kidney Diseases ◽  
Early Stage ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Treatment Efficiency ◽  
Significant Treatment ◽  
Targeted Drug Delivery Systems

Kidney diseases have gradually become a global health burden. Along with the development of nanotechnology, many hybrids or nanomaterials have been utilized to promote treatment efficiency with negligible side effects. These therapeutic agents have been successfully applied in many fields. In particular, some efforts have also been made to ameliorate the treatment of kidney diseases through targeted delivery nanomaterials. Though most of the delivery systems have not yet been transmitted into clinical use or even still at an early stage, they have shown great potential in carrying immunosuppressants like tacrolimus and triptolide, antioxidants, or siRNAs. Excitingly, some of them have achieved significant treatment effectiveness and reduced systemic side effect in kidney disease animal models. Here, we have reviewed the recent advances and presented nanotherapeutic devices designed for kidney targeted delivery.

scholarly journals Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 347
Author(s):  
Dibyendu Dana ◽  
Tuhin Das ◽  
Athena Choi ◽  
Ashif I. Bhuiyan ◽  
Tirtha K. Das ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Cancer Metastasis ◽  
Kidney Diseases ◽  
Chromosome Instability ◽  
Tumor Development ◽  
Cancer Therapeutics ◽  
Human Diseases ◽  
Cellular Processes ◽  
Anti Cancer

Cell cycle kinases represent an important component of the cell machinery that controls signal transduction involved in cell proliferation, growth, and differentiation. Nek2 is a mitotic Ser/Thr kinase that localizes predominantly to centrosomes and kinetochores and orchestrates centrosome disjunction and faithful chromosomal segregation. Its activity is tightly regulated during the cell cycle with the help of other kinases and phosphatases and via proteasomal degradation. Increased levels of Nek2 kinase can promote centrosome amplification (CA), mitotic defects, chromosome instability (CIN), tumor growth, and cancer metastasis. While it remains a highly attractive target for the development of anti-cancer therapeutics, several new roles of the Nek2 enzyme have recently emerged: these include drug resistance, bone, ciliopathies, immune and kidney diseases, and parasitic diseases such as malaria. Therefore, Nek2 is at the interface of multiple cellular processes and can influence numerous cellular signaling networks. Herein, we provide a critical overview of Nek2 kinase biology and discuss the signaling roles it plays in both normal and diseased human physiology. While the majority of research efforts over the last two decades have focused on the roles of Nek2 kinase in tumor development and cancer metastasis, the signaling mechanisms involving the key players associated with several other notable human diseases are highlighted here. We summarize the efforts made so far to develop Nek2 inhibitory small molecules, illustrate their action modalities, and provide our opinion on the future of Nek2-targeted therapeutics. It is anticipated that the functional inhibition of Nek2 kinase will be a key strategy going forward in drug development, with applications across multiple human diseases.

scholarly journals Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney

2021 ◽  
Vol 22 (14) ◽  
pp. 7679
Author(s):  
Olga Martinez-Arroyo ◽  
Estela Selma-Soriano ◽  
Ana Ortega ◽  
Raquel Cortes ◽  
Josep Redon
Keyword(s):  
Vesicle Trafficking ◽  
Neurological Diseases ◽  
Kidney Cells ◽  
Rab Gtpases ◽  
Mice Model ◽  
Cellular Processes ◽  
Intracellular Vesicle ◽  
Drosophila Model ◽  
Cardiac Fiber ◽  
Cancer And Inflammation

Small Rab GTPases, the largest group of small monomeric GTPases, regulate vesicle trafficking in cells, which are integral to many cellular processes. Their role in neurological diseases, such as cancer and inflammation have been extensively studied, but their implication in kidney disease has not been researched in depth. Rab3a and its effector Rabphillin-3A (Rph3A) expression have been demonstrated to be present in the podocytes of normal kidneys of mice rats and humans, around vesicles contained in the foot processes, and they are overexpressed in diseases with proteinuria. In addition, the Rab3A knockout mice model induced profound cytoskeletal changes in podocytes of high glucose fed animals. Likewise, RphA interference in the Drosophila model produced structural and functional damage in nephrocytes with reduction in filtration capacities and nephrocyte number. Changes in the structure of cardiac fiber in the same RphA-interference model, open the question if Rab3A dysfunction would produce simultaneous damage in the heart and kidney cells, an attractive field that will require attention in the future.

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