scholarly journals Neutrophil gelatinase-associated lipocalin as a survival factor

2005 ◽  
Vol 391 (2) ◽  
pp. 441-448 ◽  
Author(s):  
Zhimin Tong ◽  
Xuli Wu ◽  
Dmitriy Ovcharenko ◽  
Jiuxiang Zhu ◽  
Ching-Shih Chen ◽  
...  
Keyword(s):  
Survival Function ◽  
A549 Cells ◽  
Specific Effect ◽  
Mrna Levels ◽  
Mcf7 Cells ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
A Cell ◽  
Induced Apoptosis ◽  
Neutrophil Gelatinase ◽  
Interfering Rna

NGAL (human neutrophil gelatinase-associated lipocalin) and its mouse analogue 24p3 are members of the lipocalin family of small secreted proteins. These proteins are up-regulated in a number of pathological conditions, including cancers, and may function as transporters of essential factors. Although previous publications have suggested that 24p3 has pro-apoptotic functions, other data are more suggestive of a survival function. The current study was designed to determine whether NGAL is pro- or anti-apoptotic. Apoptosis induced in human adenocarcinoma A549 cells by the 5-lipoxygenase-activating-protein inhibitor MK886, or several celecoxib-derived PDK1 (phosphoinositide-dependent kinase 1) inhibitors that are devoid of cyclo-oxygenase-2 inhibitory activity, was accompanied by a dose- and time-dependent increase of NGAL mRNA levels, as was reported previously with 24p3. A similar induction of NGAL mRNA was observed in human breast cancer MCF7 cells treated with MK886, indicating this was not a cell-specific effect. Treatment of A549 cells with up to 150 μg/106 cells of purified recombinant NGAL protein had no effect on viability, whereas antisera against the full-length NGAL protein induced apoptosis in these cells. The stable overexpression of NGAL in A549 cells had no effect on proliferation or viability. However, the cell death induced by a PDK1 inhibitor was reduced by 50% in NGAL-overexpressing cells. Decreasing NGAL mRNA and protein expression with siRNA (small interfering RNA) in A549 cells increased the toxicity of a PDK1 inhibitor by approx. 45%. These data indicate that, although the induction of NGAL correlates with apoptosis, this induction represents a survival response. Because NGAL is a secreted protein, it may play an extracellular role in cell defence against toxicants and/or facilitate the survival of the remaining cells.

Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells

2005 ◽  
Vol 288 (1) ◽  
pp. L52-L60 ◽  
Author(s):  
Wenju Lu ◽  
Erik P. Lillehoj ◽  
K. Chul Kim
Keyword(s):  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Mucus Production ◽  
Mucin Production ◽  
Proinflammatory Mediators ◽  
A Cell ◽  
The Stability

Mucus hypersecretion associated with airway inflammation is reduced by glucocorticoids. Two mechanisms of glucocorticoid-mediated inhibition of mucus production have been proposed, direct inhibition of mucus production by airway epithelial cells and indirectly through inhibition of proinflammatory mediators that stimulate mucus production. In this study, we examined the effect of dexamethasone (DEX) on mRNA expression and synthesis of MUC5AC by A549 human lung adenocarcinoma cells as well as Muc5ac and total high-molecular-weight (HMW) mucins by primary rat tracheal surface epithelial (RTSE) cells. Our results showed that in primary RTSE cells, DEX 1) dose dependently suppressed Muc5ac mRNA levels, but the levels of cellular Muc5ac protein and HMW mucins were unaffected; 2) did not affect constitutive or UTP-stimulated mucin secretion; 3) enhanced the translation of Muc5ac; and 4) increased the stability of intracellular Muc5ac protein by a mechanism other than the inhibition of the proteasomal degradation. In A549 cells, however, DEX suppressed both MUC5AC mRNA levels and MUC5AC protein secretion in a dose-dependent manner. We conclude that whereas DEX inhibits the levels of Muc5ac mRNA in primary RTSE cells, the levels of Muc5ac protein remain unchanged as a consequence of increases in both translation and protein stability. Interestingly, some of the effects of DEX were opposite in a cell line.

scholarly journals Neutrophil gelatinase–associated lipocalin mediates 13-cis retinoic acid–induced apoptosis of human sebaceous gland cells

2008 ◽  
Vol 118 (4) ◽  
pp. 1468-1478 ◽  
Author(s):  
Amanda M. Nelson ◽  
Wei Zhao ◽  
Kathryn L. Gilliland ◽  
Andrea L. Zaenglein ◽  
Wenlei Liu ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Sebaceous Gland ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Gland Cells ◽  
Induced Apoptosis ◽  
Neutrophil Gelatinase ◽  
Human Sebaceous Gland

Docosahexaenoic acid induces ciap1 mRNA and protects human endothelial cells from stress-induced apoptosis

2006 ◽  
Vol 290 (6) ◽  
pp. H2178-H2186 ◽  
Author(s):  
Claudia A. Pfrommer ◽  
Wolfgang Erl ◽  
Peter C. Weber
Keyword(s):  
Fatty Acids ◽  
Endothelial Cells ◽  
Docosahexaenoic Acid ◽  
Vascular Diseases ◽  
Annexin V ◽  
Mrna Levels ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Induced Apoptosis ◽  
Interfering Rna

Induction of apoptosis represents a potential reaction of endothelial cells (ECs) after injury of the vascular endothelium. Beneficial effects of n–3 polyunsaturated fatty acids (PUFAs) in vascular diseases are widely recognized although the responsible mechanisms are not fully understood. Because it is not known whether PUFAs modulate EC apoptosis, we investigated the effects of n–3 and n–6 PUFAs on 4-hydroxynonenal (HNE)-induced EC apoptosis by annexin V staining and caspase-3 activation assays. Pretreatment with the n–3 fatty acid docosahexaenoic acid (DHA) reduced HNE-induced EC apoptosis. DHA-treated cells did not show the pronounced drop in intracellular GSH after HNE exposure seen in vehicle- or n–6 arachidonic acid-treated cells. This is most likely due to increased GSH levels in DHA-treated cells. Furthermore, DHA pretreatment increased ciap1 mRNA levels and transfection of cIAP1 small interfering RNA abolished the protective effect of DHA in HNE-induced apoptosis in HUVECs. Thus pretreatment of HUVECs with DHA reduces HNE-induced oxidative stress and apoptosis, and the protective effects of DHA seem to be dependent on cIAP1. The results provide a possible new mechanism for the atheroprotective effects of n–3 fatty acids in vascular disease.

scholarly journals Evidence for Involvement of BH3-Only Proapoptotic Members in Adenovirus-Induced Apoptosis

2007 ◽  
Vol 81 (19) ◽  
pp. 10486-10495 ◽  
Author(s):  
T. Subramanian ◽  
S. Vijayalingam ◽  
Elena Lomonosova ◽  
Ling-jun Zhao ◽  
G. Chinnadurai
Keyword(s):  
Viral Infection ◽  
Mammalian Cells ◽  
Mrna Levels ◽  
Apoptosis Pathway ◽  
Reverse Transcription Pcr ◽  
Efficient Suppression ◽  
Degradation Analysis ◽  
Infected Cells ◽  
Induced Apoptosis ◽  
Interfering Rna

ABSTRACT Mammalian cells infected with human adenoviruses (Ads) undergo an apoptotic response as a result of expression of the viral E1A proteins, and this process is suppressed by the viral E1B-19K protein. The intermediary steps in the Ad-induced apoptosis pathway are not fully resolved. The apical step in the canonical mammalian apoptosis pathway involves functional activation of one or more of the BH3-only BCL-2 family proapoptotic proteins. Previous reports have suggested that Ad-induced apoptosis may be initiated at checkpoints downstream of the BH3-only proteins. Here, we undertook genetic and biochemical studies to determine the roles of BH3-only proteins in Ad-induced apoptosis. We examined the activities of the cellular antiapoptosis protein BCL-xL and its mutants expressed from the E1B region of the Ad5 genome. Our results showed efficient suppression of Ad-induced apoptosis by a BCL-xL mutant (mt1) deficient in interaction with multidomain proapoptotic proteins BAX and BAK but proficient in interaction with BH3-only proteins, suggesting a role for BH3-only proteins in the initiation of Ad-induced apoptosis. Further, the antiapoptotic activity of BCL-xL mt1 in Ad-infected cells was observed in spite of BAK activation as a consequence of MCL-1 degradation. Analysis of the mRNA levels of various BH3-only members by reverse transcription-PCR revealed prominent activation of the Bik gene. Further, the BIK protein was also modified into an apoptotically enhanced phosphorylated form during the viral infection. In addition to BIK, enhanced level of BIM was observed in Ad-infected cells. Between the two major E1A proteins coded by the 12S and 13S mRNAs, the 13S product appeared to contribute to the activation of these BH3-only members and apoptosis during viral infection. Depletion of BIK by the use of small interfering RNA reduced the level of Ad-induced apoptosis. Our results are consistent with a model that activation of the BH3-only members may initiate Ad-induced apoptosis.

Sign in / Sign up

Export Citation Format

Share Document