scholarly journals The Role of MAPK in Drug-Induced Kidney Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Hilary Cassidy ◽  
Robert Radford ◽  
Jennifer Slyne ◽  
Sein O’Connell ◽  
Craig Slattery ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Cellular Responses ◽  
Drug Induced ◽  
Mapk Signalling ◽  
Transmission Of Information ◽  
Different Types ◽  
Mitogen Activated Protein ◽  
External Stimuli ◽  
Effective Transmission

This paper focuses on the role that mitogen-activated protein kinases (MAPKs) play in drug-induced kidney injury. The MAPKs, of which there are four major classes (ERK, p38, JNK, and ERK5/BMK), are signalling cascades which have been found to be broadly conserved across a wide variety of organisms. MAPKs allow effective transmission of information from the cell surface to the cytosolic or nuclear compartments. Cross talk between the MAPKs themselves and with other signalling pathways allows the cell to modulate responses to a wide variety of external stimuli. The MAPKs have been shown to play key roles in both mediating and ameliorating cellular responses to stress including xenobiotic-induced toxicity. Therefore, this paper will discuss the specific role of the MAPKs in the kidney in response to injury by a variety of xenobiotics and the potential for therapeutic intervention at the level of MAPK signalling across different types of kidney disease.

scholarly journals Acute interstitial nephritis and drug-induced systemic lupus erythematosus due to chlorthalidone and amiodarone: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091002 ◽  
Author(s):  
Umut Selamet ◽  
Ramy M Hanna ◽  
Anthony Sisk ◽  
Lama Abdelnour ◽  
Lena Ghobry ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Interstitial Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Systemic Lupus ◽  
Drug Induced ◽  
Systemic Manifestations

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sônia A. L. Corrêa ◽  
Katherine L. Eales
Keyword(s):  
Neurodegenerative Diseases ◽  
P38 Mapk ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Mechanisms ◽  
Cellular Localisation ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Normal Ageing ◽  
Actin Remodelling

A significant amount of evidence suggests that the p38-mitogen-activated protein kinase (MAPK) signalling cascade plays a crucial role in synaptic plasticity and in neurodegenerative diseases. In this review we will discuss the cellular localisation and activation of p38 MAPK and the recent advances on the molecular and cellular mechanisms of its substrates: MAPKAPK 2 (MK2) and tau protein. In particular we will focus our attention on the understanding of the p38 MAPK-MK2 and p38 MAPK-tau activation axis in controlling neuroinflammation, actin remodelling and tau hyperphosphorylation, processes that are thought to be involved in normal ageing as well as in neurodegenerative diseases. We will also give some insight into how elucidating the precise role of p38 MAPK-MK2 and p38 MAPK-tau signalling cascades may help to identify novel therapeutic targets to slow down the symptoms observed in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

scholarly journals New Frontiers: Approaches to Understand the Mechanistic Basis of Renal Toxicity

2018 ◽  
Vol 46 (8) ◽  
pp. 1002-1005
Author(s):  
Mary B. Nabity ◽  
Joseph W. Polli ◽  
Vishal Vaidya ◽  
Andrzej Krolewski ◽  
Warren E. Glaab
Keyword(s):  
Renal Toxicity ◽  
Kidney Injury ◽  
Scientific Session ◽  
Diabetic Patients ◽  
Drug Induced ◽  
Research Areas ◽  
Novel Biomarkers ◽  
Mechanistic Basis ◽  
New Research

A scientific session entitled “New Frontiers: Approaches to Understand the Mechanistic Basis of Renal Toxicity” focused on novel biomarkers to monitor kidney injury both preclinically and clinically, as well as providing mechanistic insight of the induced injury. Further, the role and impact of kidney membrane transporters in drug-induced kidney toxicity provided additional considerations when understanding kidney injury and the complex role of drug transporters in either sensitivity or resistance to drug-induced injury. The onset of nephropathy in diabetic patients was also presented, focusing on the quest to discover novel biomarkers that would differentiate diabetic populations more susceptible to nephropathy and renal failure. The session highlighted exciting new research areas and novel biomarkers that will enhance our understanding of kidney injury and provide tools for ensuring patient safety clinically.

scholarly journals Activation of a Mitogen-Activated Protein Kinase Hog1 by DNA Damaging Agent Methyl Methanesulfonate in Yeast

2020 ◽  
Vol 7 ◽  
Author(s):  
Shan Huang ◽  
David Zhang ◽  
Fangli Weng ◽  
Yuqi Wang
Keyword(s):  
Protein Kinase ◽  
Cellular Responses ◽  
Mitogen Activated Protein Kinase ◽  
Yeast Cells ◽  
Methyl Methanesulfonate ◽  
Regulate Gene Expression ◽  
Dna Damaging Agents ◽  
Mitogen Activated Protein ◽  
Regulate Gene

Hog1 is a mitogen-activated protein kinase in yeast that primarily regulates cellular responses to hyperosmolarity stress. In this study, we have examined the potential involvement of Hog1 in mediating cellular responses to DNA damaging agents. We find that treatment of yeast cells with DNA damaging agent methyl methanesulfonate (MMS) induces a marked and prolonged Hog1 activation. Distinct from stressors such as arsenite that activates Hog1 via inhibiting its phosphatases, activation of Hog1 by MMS is phosphatase-independent. Instead, MMS impairs a critical phosphor-relay process that normally keeps Hog1 in an inactive state. Functionally, MMS-activated Hog1 is not translocated to the nucleus to regulate gene expression but rather stays in the cytoplasm and regulates MMS-induced autophagy and cell adaptation to MMS stress. These findings reveal a new role of Hog1 in regulating MMS-induced cellular stress.

scholarly journals Cellular Responses to Proteasome Inhibition: Molecular Mechanisms and Beyond

2019 ◽  
Vol 20 (14) ◽  
pp. 3379 ◽  
Author(s):  
Nicolas Albornoz ◽  
Hianara Bustamante ◽  
Andrea Soza ◽  
Patricia Burgos
Keyword(s):  
Side Effects ◽  
Inclusion Bodies ◽  
Molecular Mechanisms ◽  
Proteasome Inhibitors ◽  
Proteasome Inhibition ◽  
Cellular Responses ◽  
Cell Responses ◽  
Different Types ◽  
Inflammatory Processes

Proteasome inhibitors have been actively tested as potential anticancer drugs and in the treatment of inflammatory and autoimmune diseases. Unfortunately, cells adapt to survive in the presence of proteasome inhibitors activating a variety of cell responses that explain why these therapies have not fulfilled their expected results. In addition, all proteasome inhibitors tested and approved by the FDA have caused a variety of side effects in humans. Here, we describe the different types of proteasome complexes found within cells and the variety of regulators proteins that can modulate their activities, including those that are upregulated in the context of inflammatory processes. We also summarize the adaptive cellular responses activated during proteasome inhibition with special emphasis on the activation of the Autophagic-Lysosomal Pathway (ALP), proteaphagy, p62/SQSTM1 enriched-inclusion bodies, and proteasome biogenesis dependent on Nrf1 and Nrf2 transcription factors. Moreover, we discuss the role of IRE1 and PERK sensors in ALP activation during ER stress and the involvement of two deubiquitinases, Rpn11 and USP14, in these processes. Finally, we discuss the aspects that should be currently considered in the development of novel strategies that use proteasome activity as a therapeutic target for the treatment of human diseases.

scholarly journals Regulation of signalling by microRNAs

2012 ◽  
Vol 40 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Roi Avraham ◽  
Yosef Yarden
Keyword(s):  
Transcriptional Repression ◽  
Signal Propagation ◽  
Cellular Responses ◽  
Mirna Biogenesis ◽  
Extracellular Signals ◽  
Genetic Switches ◽  
Control Stability ◽  
External Stimuli ◽  
Mirna Biogenesis Pathway

Stringent regulation of biochemical signalling pathways involves feedback and feedforward loops, which underlie robust cellular responses to external stimuli. Regulation occurs in all horizontal layers of signalling networks, primarily by proteins that mediate internalization of receptor–ligand complexes, dephosphorylation of kinases and their substrates, as well as transcriptional repression. Recent studies have unveiled the role of miRNAs (microRNAs), post-transcriptional regulators that control mRNA stability, as key modulators of signal propagation. By acting as genetic switches or fine-tuners, miRNAs can directly and multiply regulate cellular outcomes in response to diverse extracellular signals. Conversely, signalling networks temporally control stability, biogenesis and abundance of miRNAs, by regulating layers of the miRNA biogenesis pathway. In the present mini-review, we use a set of examples to illustrate the extensive interdependence between miRNAs and signalling networks.

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