AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration

Herdegen, Thomas; Waetzig, Vicki

doi:10.1038/sj.onc.1204387

Cited by 187 publications

(131 citation statements)

References 132 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…The results, while confirming distinct requirements for the induction of the two MAP kinases in different forms of neuronal apoptotic death [22], at the same time need further studies to elucidate the down-regulation/ inhibition of p38 MAPK observed upon JNK activation. Our results are also in agreement with several observations suggesting that JNK is involved in neuronal cell death during early brain development [23], in neurodegenerative disorders [24] or under oxidative insult [25].…”

Section: Discussionsupporting

confidence: 93%

Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells

Filomeni

Aquilano

Civitareale

et al. 2005

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Changes in intracellular redox status are crucial events that trigger downstream proliferation or death responses through activation of specific signaling pathways. Moreover, cell responses to oxidative challenge may depend on the pattern of redox-sensitive molecular factors. The stress-activated protein kinases c-Jun-N-terminal kinase (JNK) and p38 MAP kinase (p38 MAPK ) are implicated in different forms of apoptotic neuronal cell death. Here, we investigated the effects, on neuroblastoma cells, of the prooxidant molecule GSSG, which we previously demonstrated to be an efficient proapoptotic compound able to activate the p38 MAPK death pathway in promonocytic cells. We found that neuroblastoma cells are not prone to GSSG-induced apoptosis, although the treatment slightly induced growth arrest through the accumulation of p53 and its downstream target gene, p21. However, GSSG treatment became cytotoxic when cells were previously depleted of intracellular GSH content. Under this condition, apoptosis was triggered by an increased production of superoxide that led to a specific activation of the JNK-dependent pathway. The involvement of superoxide and JNK was demonstrated by cell death inhibition in experiments carried out in the presence of Cu,Zn superoxide dismutase or with specific inhibitors of JNK activity. Our data give support to the studies that indicate preferential requirements for the involvement of stress-activated kinases in apoptotic neuronal cells.

show abstract

Section: Discussionsupporting

confidence: 93%

Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells

Filomeni

Aquilano

Civitareale

et al. 2005

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…Because lamin A/C sequesters cFos at the nuclear envelope of fibroblasts and suppresses the DNA binding activity of transcription activator protein-1 (AP-1) by affecting cFos and cJun dimerization [3], reduced levels of lamin protein could have consequences on downstream transcription. If AV nodal myocytes, like other excitable neural cells, are particularly sensitive to AP-1 mediated transcriptional regulation, including caspase activation and stress-induced apoptosis [41], mutations that reduce lamin A/C levels could activate pro-cell death signals selectively in these specialized myocytes.…”

Section: Discussionmentioning

confidence: 99%

Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease

Wolf

Wang

Alcalai

et al. 2008

Journal of Molecular and Cellular Cardiology

152

147

View full text Add to dashboard Cite

Mutations in the lamin A/C (LMNA) gene, which encodes nuclear membrane proteins, cause a variety of human conditions including dilated cardiomyopathy (DCM) with associated cardiac conduction system disease. To investigate mechanisms responsible for electrophysiologic and myocardial phenotypes caused by dominant human LMNA mutations, we performed longitudinal evaluations in heterozygous Lmna +/-mice. Despite one normal allele, Lmna +/-mice had 50% of normal cardiac lamin A/C levels and developed cardiac abnormalities. Conduction system function was normal in neonatal Lmna +/-mice but by 4 weeks of age AV nodal myocytes had abnormally shaped nuclei and active apoptosis. Telemetric and in vivo electrophysiologic studies in 10 week-old Lmna +/-mice showed atrioventricular (AV) conduction defects and both atrial and ventricular arrhythmias, analogous to those observed in humans with heterozygous LMNA mutations. Isolated myocytes from 12-month old Lmna +/-mice exhibited impaired contractility. In vivo cardiac studies of aged Lmna +/-mice revealed DCM; in some mice this occurred without Contact address: Charles I. Berul, M.D., Department of Cardiology -Children's Hospital, 300 Longwood Ave., Boston, MA 02115 USA, Phone: 617 355-6432, Fax: 617 566-5671, charles.berul@cardio.chboston.org. * These authors contributed equally to this publication. Disclosures: NonePublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public AccessAuthor Manuscript J Mol Cell Cardiol. Author manuscript; available in PMC 2010 December 29. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript overt conduction system disease. However, neither histopathology nor serum CK levels indicated skeletal muscle pathology. These data demonstrate cardiac pathology due to heterozygous Lmna mutations reflecting a 50% reduction in lamin protein levels. Lamin haploinsufficiency caused early-onset programmed cell death of AV nodal myocytes and progressive electrophysiologic disease. While lamin haploinsufficiency was better tolerated by non-conducting myocytes, ultimately these too succumbed to diminished lamin levels leading to dilated cardiomyopathy, which presumably arose independently from conduction system disease.

show abstract

“…These dimers bind to specific DNA regions, the AP-1 domains, which regulate the expression of a number of target genes (collectively referred to as late response genes). 161 Like NF-B, the activation of AP-1 in microglia drives a proinflammatory response and the release of several cytotoxic agents. [162][163][164] …”

Section: Nf-b and Ap-1mentioning

confidence: 99%

Microglial Activation in Stroke: Therapeutic Targets

2010

View full text Add to dashboard Cite

Summary:Microglial activation is an early response to brain ischemia and many other stressors. Microglia continuously monitor and respond to changes in brain homeostasis and to specific signaling molecules expressed or released by neighboring cells. These signaling molecules, including ATP, glutamate, cytokines, prostaglandins, zinc, reactive oxygen species, and HSP60, may induce microglial proliferation and migration to the sites of injury. They also induce a nonspecific innate immune response that may exacerbate acute ischemic injury. This innate immune response includes release of reactive oxygen species, cytokines, and proteases. Microglial activation requires hours to days to fully develop, and thus presents a target for therapeutic intervention with a much longer window of opportunity than acute neuroprotection. Effective agents are now available for blocking both microglial receptor activation and the microglia effector responses that drive the inflammatory response after stroke. Effective agents are also available for targeting the signal transduction mechanisms linking these events. However, the innate immune response can have beneficial as well deleterious effects on outcome after stoke, and a challenge will be to find ways to selectively suppress the deleterious effects of microglial activation after stroke without compromising neurovascular repair and remodeling.

show abstract

AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration

Cited by 187 publications

References 132 publications

Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells

Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells

Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease

Microglial Activation in Stroke: Therapeutic Targets

Contact Info

Product

Resources

About