Signal transduction by serine proteinases in astrocytes: Regulation of proliferation, morphologic changes, and survival via proteinase‐activated receptors

Wang, Hong; Reiser, Georg

doi:10.1002/ddr.10319

Cited by 7 publications

(10 citation statements)

References 54 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The regional distribution of the neuronal lesions reflects that of the GluR distribution. Astrocytes with swollen perikarya and karyorrhexis have often been observed in the vicinity of these lesions [8][9]. It has been suggested that astrocytes contribute to a decline of neurologic function by either the accumulation and release of EAAs after ischemia and oxidative stress or by formation of epileptogenic scars in response to CNS injury and metabolism of protoxins to potent toxins.…”

Section: Introductionmentioning

confidence: 99%

Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

Gill

2008

Mar. Drugs

View full text Add to dashboard Cite

Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes-GFAP and the glutamate receptors including GluR 2, NMDAR 1, NM-DAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk), and apoptotic genes were altered. The chemokines that were up-regulated included -IL1-α, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest Mar. Drugs 2008, 6(1) 26 that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity.

show abstract

Section: Introductionmentioning

confidence: 99%

Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

Gill

2008

Mar. Drugs

View full text Add to dashboard Cite

show abstract

“…PI-PLC d3 also has been identified in many histotypes at low concentrations [Pawelczyk and Matecki, 1998]; PI-PLC d4 is expressed in the brain as well as in regenerating tissues [Pawelczyk, 1999]; PI-PLC g1 is expressed in keratinocytes and foetal cartilage [Ananthanarayanan et al, 2002] and has been found almost exclusively in the cytoplasm [McBride et al, 1991;Diakonova et al, 1997]; also PI-PLC e occurs in many tissues [Wing et al, 2003]. Notwithstanding the growing interest for the role played by the PI-PLC family enzymes in the nervous system [Ledeen and Wu, 2004], no definitive studies have been accomplished in glial cells [Choi et al, 1989;Tallant and Higson, 1997;Wang and Reiser, 2003]. As a matter of fact the inositol lipid cycle seems to be involved in glial activation during neurodegenerative processes [Vitale et al, 2004].…”

mentioning

confidence: 99%

Expression of phosphoinositide‐specific phospholipase C isoenzymes in cultured astrocytes

Vasco¹,

Fabrizi²,

Artico³

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

Signal transduction from plasma membrane to cell nucleus is a complex process depending on various components including lipid signaling molecules, in particular phosphoinositides and their related enzymes, which act at cell periphery and/or plasma membrane as well as at nuclear level. As far as the nervous system may concern the inositol lipid cycle has been hypothesized to be involved in numerous neural as well as glial functions. In this context, however, a precise panel of glial PLC isoforms has not been determined yet. In the present experiments we investigated astrocytic PLC isoforms in astrocytes obtained from foetal primary cultures of rat brain and from an established cultured (C6) rat astrocytoma cell line, two well known cell models for experimental studies on glia. Identification of PLC isoforms was achieved by using a combination of RT-PCR and immunocytochemistry experiments. While in both cell models the most represented PI-PLC isoforms were beta4, gamma1, delta4, and epsilon, isoforms PI-PLC beta2 and delta3 were not detected. Moreover, in primary astrocyte cultures PI-PLC delta3 resulted well expressed in C6 cells but was absent in astrocytes. Immunocytochemistry performed with antibodies against specific PLC isoforms substantially confirmed this pattern of expression both in astrocytes and C6 glioma cells. In particular while some isoenzymes (namely isoforms beta3 and beta4) resulted mainly nuclear, others (isoforms delta4 and epsilon) were preferentially localized at cytoplasmic and plasma membrane level.

show abstract

“…2005). In the nervous system, PAR‐2 is widely expressed in brain, spinal cord, and peripheral nerves (Wang and Reiser 2003a,b; Bushell et al. 2006).…”

mentioning

confidence: 99%

Phosphorylation of Ser45 and Ser59 of αB‐crystallin and p38/extracellular regulated kinase activity determine αB‐crystallin‐mediated protection of rat brain astrocytes from C2‐ceramide‐ and staurosporine‐induced cell death

Li¹,

Reiser²

2011

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

J. Neurochem. (2011) 118, 354–364. Abstract We previously demonstrated that αB‐crystallin and protease‐activated receptor (PAR) are involved in protection of astrocytes against C2‐ceramide‐ and staurosporine‐induced cell death [Li et al. (2009) J. Neurochem.110, 1433–1444]. Here, we further investigated the mechanism of cytoprotection by αB‐crystallin. Our current data revealed that after down‐regulation of αB‐crystallin by siRNA, cell death caused by C2‐ceramide and staurosporine is increased. Furthermore, we investigated the mechanism of cytoprotection of astrocytes by intracellular αB‐crystallin. Application of specific inhibitors of p38 and extracellular regulated kinase (ERK) abrogates the protection of astrocytes by over‐expression of αB‐crystallin. Thus, p38 and ERK contribute to protective processes by αB‐crystallin. To reveal the molecular mechanism of αB‐crystallin‐mediated cytoprotection, we mimicked phosphorylation or unphosphorylation of αB‐crystallin. In these experiments, we found that the phosphorylation of αB‐crystallin at Ser45 and Ser59 is required for protection. Ser19 phosphorylation of αB‐crystallin does not contribute to protection. Moreover, we detected that PAR‐2 activation increases the phosphorylation level of αB‐crystallin at Ser59, but does not affect the expression level of αB‐crystallin. Thus, endogenous αB‐crystallin has protective capacity employing a mechanism, which involves regulation of the phosphorylation status of αB‐crystallin and p38 and ERK activity. Moreover, we report that PAR‐2 activation evokes the phosphorylation of αB‐crystallin to increase astrocytes survival.

show abstract

Signal transduction by serine proteinases in astrocytes: Regulation of proliferation, morphologic changes, and survival via proteinase‐activated receptors

Cited by 7 publications

References 54 publications

Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

Expression of phosphoinositide‐specific phospholipase C isoenzymes in cultured astrocytes

Phosphorylation of Ser45 and Ser59 of αB‐crystallin and p38/extracellular regulated kinase activity determine αB‐crystallin‐mediated protection of rat brain astrocytes from C2‐ceramide‐ and staurosporine‐induced cell death

Contact Info

Product

Resources

About