p38 MAPK in regulating cellular responses to ultraviolet radiation

Li, Jinlian; Zhou, Yingbin; Wang, Chunbo

doi:10.1007/s11373-007-9148-4

Cited by 69 publications

(63 citation statements)

References 102 publications

(104 reference statements)

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“…To determine whether enhanced apoptosis is a more general phenomenon of p38 inhibition, we tested 2 non-ER stress-mediated apoptotic inducers: staurosporine and UV irradiation (2). While p38 inhibition enhanced macrophage apoptosis in cells treated with staurosporine ( Figure 6F), apoptosis was suppressed in cells exposed to UV irradiation ( Figure 6G), consistent with previous reports of a proapoptotic role for p38 (34). In contrast, p38 has previously been shown to protect from pathogen-induced apoptosis (24,35,36).…”

Section: Macrophage P38α Deficiency Leads To Enhanced Macrophage Apopsupporting

confidence: 90%

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Macrophage deficiency of p38α MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice

Seimon¹,

Wang²,

Han³

et al. 2009

J. Clin. Invest.

113

127

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ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stress-induced apoptosis may affect advanced atherosclerosis. Here we placed Apoe -/-mice deficient in macrophage p38α MAPK on a Western diet and found that they had a marked increase in macrophage apoptosis and plaque necrosis. The macrophage p38α-deficient lesions also exhibited a significant reduction in collagen content and a marked thinning of the fibrous cap, which suggests that plaque progression was advanced in these mice. Consistent with our in vivo data, we found that ER stress-induced apoptosis in cultured primary mouse macrophages was markedly accelerated under conditions of p38 inhibition. Pharmacological inhibition or genetic ablation of p38 suppressed activation of Akt in cultured macrophages and in atherosclerotic lesions. In addition, inhibition of Akt enhanced ER stress-induced macrophage apoptosis, and expression of a constitutively active myristoylated Akt blocked the enhancement of ER stress-induced apoptosis that occurred with p38 inhibition in cultured cells. Our results demonstrate that p38α MAPK may play a critical role in suppressing ER stress-induced macrophage apoptosis in vitro and advanced lesional macrophage apoptosis in vivo.

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Section: Macrophage P38α Deficiency Leads To Enhanced Macrophage Apopsupporting

confidence: 90%

“…Several previous studies have shown that activation of p38 MAPK can have pro-or antiapoptotic effects depending on the cellular environment (2,23,24,(34)(35)(36). The important finding in the present study is that in advanced atherosclerotic plaque, p38α plays a prosurvival role in macrophages.…”

Section: Discussionsupporting

confidence: 63%

Macrophage deficiency of p38α MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice

Seimon¹,

Wang²,

Han³

et al. 2009

J. Clin. Invest.

113

127

View full text Add to dashboard Cite

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“…Finally, we observed a moderate but significant decrease in annexin V-positive staining at 72 h post-UV in SB202190-treated HDLFs (Fig. 6B), supporting a proapoptotic role for p38␣/␤ in UV-irradiated HDLFs, as previously observed in various cell lines (31). In addition, sub-G 1 peak analysis consistently revealed a slight reduction in UV-induced apoptosis in SB202190-treated cells, although this was not statistically significant (Fig.…”

Section: Effects Of Mapk Inactivation On Cell Death and Proliferationsupporting

confidence: 84%

A Sensitive Flow Cytometry-based Nucleotide Excision Repair Assay Unexpectedly Reveals That Mitogen-activated Protein Kinase Signaling Does Not Regulate the Removal of UV-induced DNA Damage in Human Cells

Rouget¹,

Auclair²,

Loignon

et al. 2008

Journal of Biological Chemistry

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In response to diverse genotoxic stimuli (e.g. UV and cisplatin), the mitogen-activated protein kinases ERK1/2, JNK1/2, and p38␣/␤ become rapidly phosphorylated and in turn activate multiple downstream effectors that modulate apoptosis and/or growth arrest. Furthermore, previous lines of evidence have strongly suggested that ERK1/2 and JNK1/2 participate in global-genomic nucleotide excision repair, a critical antineoplastic pathway that removes helix-distorting DNA adducts induced by a variety of mutagenic agents, including UV. To rigorously evaluate the potential role of mitogen-activated protein kinases in global-genomic nucleotide excision repair, various human cell strains (primary skin fibroblasts, primary lung fibroblasts, and HCT116 colon carcinoma cells) were treated with highly specific chemical inhibitors, which, following UV exposure, (i) abrogated the capacities of ERK1/2, JNK1/2, or p38␣/␤ to phosphorylate specific downstream effectors and (ii) characteristically modulated cellular proliferation, clonogenic survival, and/or apoptosis. A highly sensitive flow cytometry-based nucleotide excision repair assay recently optimized and validated in our laboratory was then employed to directly demonstrate that the kinetics of UV DNA photoadduct repair are highly similar in mock-treated versus mitogen-activated protein kinase inhibitor-treated cells. These data on primary and tumor cells treated with pharmacological inhibitors were fully corroborated by repair studies using (i) short hairpin RNA-mediated knockdown of ERK1/2 or JNK1/2 in human U2OS osteosarcoma cells and (ii) expression of a dominant negative p38␣ mutant in human primary lung fibroblasts. Our results provide solid evidence for the first time, in disaccord with a burgeoning perception, that mitogen-activated protein kinase signaling does not influence the efficiency of human global-genomic nucleotide excision repair.

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“…Nonetheless, we can exclude some of the possible substrates. Tumor suppressor protein p53 and CCAAT/enhancer-binding protein homologous protein, for example, can be activated by p38 MAPK and activate proapoptotic factors (Ono and Han, 2000;Shi and Gaestel, 2002;Jinlian et al, 2007). However, p53 is not detectable in J774A.1 macrophages and SMCs even after stimulation with protein synthesis inhibitors (Croons et al, 2007).…”

Section: Role Of Mapk In Anisomycin-induced Macrophage Apoptosis 863mentioning

confidence: 99%

The Protein Synthesis Inhibitor Anisomycin Induces Macrophage Apoptosis in Rabbit Atherosclerotic Plaques through p38 Mitogen-Activated Protein Kinase

Croons

Martinet²,

Herman³

et al. 2009

J Pharmacol Exp Ther

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Because macrophages play a major role in atherosclerotic plaque destabilization, selective removal of macrophages represents a promising approach to stabilize plaques. We showed recently that the protein synthesis inhibitor cycloheximide, in contrast to puromycin, selectively depleted macrophages in rabbit atherosclerotic plaques without affecting smooth muscle cells (SMCs). The mechanism of action of these two translation inhibitors is dissimilar and could account for the differential effects on SMC viability. It is not known whether selective depletion of macrophages is confined to cycloheximide or whether it can also be achieved with translation inhibitors that have a similar mechanism of action. Therefore, in the present study, we investigated the effect of anisomycin, a translation inhibitor with a mechanism of action similar to cycloheximide, on macrophage and SMC viability. In vitro, anisomycin induced apoptosis of macrophages in a concentration-dependent manner, whereas SMCs were only affected at higher concentrations. In vivo, anisomycin selectively decreased the macrophage content of rabbit atherosclerotic plaques through apoptosis. The p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole] prevented anisomycin-induced macrophage death, without affecting SMC viability. SB202190 decreased anisomycin-induced p38 MAPK phosphorylation, did not alter c-Jun NH 2 -terminal kinase (JNK) phosphorylation, and increased extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. The latter effect was abolished by the mitogenactivated protein kinase kinase 1/2 inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene ethanolate], although the prevention of anisomycin-induced macrophage death by SB202190 remained unchanged. The JNK phosphorylation inhibitor SP600125 did not affect anisomycin-induced macrophage or SMC death. In conclusion, anisomycin selectively decreased the macrophage content in rabbit atherosclerotic plaques, indicating that this effect is not confined to cycloheximide. p38 MAPK, but not ERK1/2 or JNK, plays a major role in anisomycin-induced macrophage death.

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p38 MAPK in regulating cellular responses to ultraviolet radiation

Cited by 69 publications

References 102 publications

Macrophage deficiency of p38α MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice

Macrophage deficiency of p38α MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice

A Sensitive Flow Cytometry-based Nucleotide Excision Repair Assay Unexpectedly Reveals That Mitogen-activated Protein Kinase Signaling Does Not Regulate the Removal of UV-induced DNA Damage in Human Cells

The Protein Synthesis Inhibitor Anisomycin Induces Macrophage Apoptosis in Rabbit Atherosclerotic Plaques through p38 Mitogen-Activated Protein Kinase

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