Basic Properties of the p38 Signaling Pathway in Response to Hyperosmotic Shock

Messaoud, Nabil Ben; Katzarova, Ilina; López, José Manuel

doi:10.1371/journal.pone.0135249

Cited by 22 publications

(20 citation statements)

References 39 publications

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“…We also reported the basic properties of the p38 signaling pathway in response to hyperosmotic shock by using Xenopus oocytes. The response of p38 to osmostress was ultrasensitive, bimodal, and with low hysteresis [87].…”

Section: Basic Signaling Properties Of Mapksmentioning

confidence: 96%

“…It is also possible to microinject antibodies, antisense oligonucleotides, or other molecules that cannot cross the cell membrane in order to manipulate any specific signaling pathway. Importantly, cytochrome c microinjection in Xenopus oocytes induces caspase-3 activity [140], making affordable the study of the signaling pathways activated by cythochrome c release and the positive feedback loops engaged by caspases [87,111]. Recently, by using Xenopus oocytes and egg extracts, it was demonstrated that positive feedback loops allow apoptosis to spread though the cytoplasm in self-regenerating trigger waves, which were correlated with caspase activation [141].…”

Section: Xenopus Oocytes As a Cell Model To Understand Apoptosismentioning

confidence: 99%

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Understanding MAPK Signaling Pathways in Apoptosis

Yue

López

2020

IJMS

Self Cite

694

411

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MAPK (mitogen-activated protein kinase) signaling pathways regulate a variety of biological processes through multiple cellular mechanisms. In most of these processes, such as apoptosis, MAPKs have a dual role since they can act as activators or inhibitors, depending on the cell type and the stimulus. In this review, we present the main pro- and anti-apoptotic mechanisms regulated by MAPKs, as well as the crosstalk observed between some MAPKs. We also describe the basic signaling properties of MAPKs (ultrasensitivity, hysteresis, digital response), and the presence of different positive feedback loops in apoptosis. We provide a simple guide to predict MAPKs’ behavior, based on the intensity and duration of the stimulus. Finally, we consider the role of MAPKs in osmostress-induced apoptosis by using Xenopus oocytes as a cell model. As we will see, apoptosis is plagued with multiple positive feedback loops. We hope this review will help to understand how MAPK signaling pathways engage irreversible cellular decisions.

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Section: Basic Signaling Properties Of Mapksmentioning

confidence: 96%

Section: Xenopus Oocytes As a Cell Model To Understand Apoptosismentioning

confidence: 99%

Understanding MAPK Signaling Pathways in Apoptosis

Yue

López

2020

IJMS

Self Cite

694

411

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“…Another aftermath of the astrocytic swelling is the occurrence of abnormal RVD. During RVD, astrocytes release organic osmolytes and neurotoxic substances that could cause inflammation (Cavet, Harrington, Vollmer, Ward, & Zhang, ), a hyperosmotic environment (Wang & Parpura, ), and astrocytic apoptosis and neurodegeneration (Ben Messaoud, Katzarova, & Lopez, ), thereby leading to irreversible brain damage.…”

Section: Gfap and Neurological Diseasesmentioning

confidence: 99%

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

Liu

et al. 2019

Glia

104

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Glial fibrillary acidic protein (GFAP), a type III intermediate filament, is a marker of mature astrocytes. The expression of GFAP gene is regulated by many transcription factors (TFs), mainly Janus kinase‐2/signal transducer and activator of transcription 3 cascade and nuclear factor κ‐light‐chain‐enhancer of activated B cell signaling. GFAP expression is also modulated by protein kinase and other signaling molecules that are elicited by neuronal activity and hormones. Abnormal expression of GFAP proteins occurs in neuroinflammation, neurodegeneration, brain edema‐eliciting diseases, traumatic brain injury, psychiatric disorders and others. GFAP, mainly in α‐isoform, is the major component of cytoskeleton and the scaffold of astrocytes, which is essential for the maintenance of astrocytic structure and shape. GFAP also has highly morphological plasticity because of its quick changes in assembling and polymerizing states in response to environmental challenges. This plasticity and its corresponding cellular morphological changes endow astrocytes the functions of physical barrier between adjacent neurons and stabilizer of extracellular environment. Moreover, GFAP colocalizes and even molecularly associates with many functional molecules. This feature allows GFAP to function as a platform for direct interactions between different molecules. Last, GFAP involves transportation and localization of other functional proteins and thus serves as a protein transport guide in astrocytes. This guiding role of GFAP involves an elastic retraction and extension cytoskeletal network that couples with GFAP reassembling, transporting, and membrane protein recycling machinery. This paper reviews our current understanding of the expression and functions of GFAP as well as their regulation.

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“…These four pathways, induced early by osmostress, converge on the mitochondria to trigger late cytochrome c release and caspase-3 activation (2). Moreover, we have found that caspase-3 activation induces rapid phosphorylation of p38, thus creating a positive feedback loop in osmostress-induced apoptosis (3). However, the role of Bcl-2 family members in osmostress-induced apoptosis was not addressed in previous studies.…”

mentioning

confidence: 85%

Hyperosmotic Shock Engages Two Positive Feedback Loops through Caspase-3-dependent Proteolysis of JNK1-2 and Bid

Yue

Messaoud

López

2015

Journal of Biological Chemistry

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Hyperosmotic shock induces early calpain activation, Smac/ DIABLO release from the mitochondria, and p38/JNK activation in Xenopus oocytes. These pathways regulate late cytochrome c release and caspase-3 activation. Here, we show that JNK1-1 and JNK1-2 are activated early by osmostress, and sustained activation of both isoforms accelerates the apoptotic program. When caspase-3 is activated, JNK1-2 is proteolyzed at Asp-385 increasing the release of cytochrome c and caspase-3 activity, thereby creating a positive feedback loop. Expression of Bcl-x L markedly reduces hyperosmotic shock-induced apoptosis. In contrast, expression of Bid induces rapid caspase-3 activation, even in the absence of osmostress, which is blocked by Bcl-x L co-expression. In these conditions a significant amount of Bid in the cytosol is mono-and bi-ubiquitinated. Caspase-3 activation by hyperosmotic shock induces proteolysis of Bid and mono-ubiquitinated Bid at Asp-52 increasing the release of cytochrome c and caspase-3 activation, and thus creating a second positive feedback loop. Revealing the JNK isoforms and the loops activated by osmostress could help to design better treatments for human diseases caused by perturbations in fluid osmolarity.Hyperosmotic shock induces cytochrome c release and caspase-3 activation in Xenopus oocytes (1). Recently, we have shown that hyperosmotic shock also induces rapid calpain activation and Smac/DIABLO (second mitochondrion-derived activator of caspases/direct IAP-binding protein with low PI Smac/DIABLO) release from the mitochondria, as well as p38 and JNK (c-Jun N-terminal kinase) activation. These four pathways, induced early by osmostress, converge on the mitochondria to trigger late cytochrome c release and caspase-3 activation (2). Moreover, we have found that caspase-3 activation induces rapid phosphorylation of p38, thus creating a positive feedback loop in osmostress-induced apoptosis (3). However, the role of Bcl-2 family members in osmostress-induced apoptosis was not addressed in previous studies. It is not clear which specific p38 and JNK isoforms are activated by osmostress and how they regulate the apoptotic program. Bid is a member of the BH3 2 -only proteins that plays a crucial role in regulating the permeability of the outer mitochondrial membrane. The BH3 region is required for interaction with both pro-apoptotic Bax or anti-apoptotic protein Bcl-x L (4). Bid also contains a large unstructured loop (amino acids 42-79) with a variety of sites that are subjected to post-translational modifications, regulating Bid localization and apoptotic function (5).Bid is a caspase-8 substrate, and the resulting tBid translocates to mitochondria and initiates mitochondrial protein release. The cleavage site of caspase-8 in human Bid is Asp-60 (6) and in Xenopus laevis is Asp-52 (7). Xenopus Bid can also be proteolyzed by caspase-10␤ (7). In addition, it has been reported that caspase-3 can cleave human Bid at Asp-60 (8), and cleavage sites for non-caspase proteases have been detected, such as Gly...

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Basic Properties of the p38 Signaling Pathway in Response to Hyperosmotic Shock

Cited by 22 publications

References 39 publications

Understanding MAPK Signaling Pathways in Apoptosis

Understanding MAPK Signaling Pathways in Apoptosis

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

Hyperosmotic Shock Engages Two Positive Feedback Loops through Caspase-3-dependent Proteolysis of JNK1-2 and Bid

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