Abstract:
:Hexavalent chromium (Cr[VI]) is classified by the International Agency for Research on Cancer as a group I carcinogen. Although the U.S. Occupational Safety and Health Administration was obliged to reduce the permissible exposure limit (PEL), it was reported that U.S. workers continue to be exposed to dangerously high Cr(VI) levels. In this study, we examined the role of p53 and target genes in a bronchoalveolar carcinoma isogenic cell line system and in primary human bronchial epithelial cells. p53-Negative parental H358 cell line, the same line in which the wild-type p53 expression vector (pC53-SN3) was introduced, and cells obtained from biopsies of human bronchus were exposed to chromate. Induction of DNA strand breaks were evaluated by alkaline elution assay, and apoptosis was analyzed by gel ladder, annexin V-PI staining, and ELISA, whereas p53 and target genes were evaluated by Western blots. Although Cr(VI) induced DNA strand breaks in both H358 cell clones, apoptosis was present only in the p53-transfected cells (H358p53(+/+)). In these cells, Cr(VI)-induced apoptosis is mediated by p53 upregulation of p53-upregulated modulator of apoptosis (PUMA), BAX translocation to mitochondria, cytochrome c release, and caspase-3 activation. In primary human bronchial epithelial cells expressing functional p53, Cr(VI) induced expression of PUMA and Noxa, which promote apoptosis through BAX. This result establishes p53 as the "necessary" player in Cr(VI)-induced apoptosis. To the best of our knowledge, this is the first report indicating strict correlation of Cr(VI) apoptosis to PUMA induction on primary human bronchoalveolar cells in short-term cultures.
journal_name
Am J Respir Cell Mol Biolauthors
Russo P,Catassi A,Cesario A,Imperatori A,Rotolo N,Fini M,Granone P,Dominioni Ldoi
10.1165/rcmb.2005-0213OCkeywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
589-600issue
6eissn
1044-1549issn
1535-4989pii
2005-0213OCjournal_volume
33pub_type
杂志文章abstract::Extracellular signal-regulated kinases (ERKs) phosphorylate and regulate cytoskeletal components of contractile cells and have been implicated in integrin-mediated adhesion. In this study, we examined the contributions of adherence, cell flattening, and cytoskeletal reorganization to adhesion-induced ERK activation in...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.17.4.2702
更新日期:1997-10-01 00:00:00
abstract::Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macroph...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0405OC
更新日期:2006-05-01 00:00:00
abstract::Airway inflammation, hyperreactivity, increased number of goblet cells, and mucus overproduction characterize asthma. Respiratory challenge with ovalbumin (OVA) of sensitized mice has been shown by several laboratories to cause pulmonary pathology similar to that observed in human allergic asthma. Recently, interleuki...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.22.3.3768
更新日期:2000-03-01 00:00:00
abstract::Epithelial-mesenchymal cell interactions and factors that control normal lung development are key players in lung injury, repair, and fibrosis. A number of studies have investigated the roles and sources of epithelial progenitors during lung regeneration; such information, however, is limited in lung fibroblasts. Thus...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2015-0095OC
更新日期:2016-04-01 00:00:00
abstract::While elastin degradation is a hallmark of pulmonary emphysema, it is likely that elastin synthesis also occurs. However, the supramolecular structure and function of the newly synthesized elastin are abnormal. Very little is known about the regulation of elastin synthesis during the development of emphysema when prom...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/3.4.369
更新日期:1990-10-01 00:00:00
abstract::β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the β2AR, epinephrine. In this study, ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0364OC
更新日期:2013-02-01 00:00:00
abstract::Lung endothelial cell apoptosis and injury occur throughout all stages of acute lung injury/acute respiratory distress syndrome and impact disease progression. Caspases 1, 4, and 5 are essential for completion of the apoptotic program known as pyroptosis that also involves proinflammatory cytokines. Because gasdermin ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2017-0393OC
更新日期:2018-07-01 00:00:00
abstract::Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and prolifer...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0225OC
更新日期:2017-04-01 00:00:00
abstract::The human lung is constantly exposed to the environment and potential pathogens. As the interface between host and environment, the respiratory epithelium has evolved sophisticated sensing mechanisms as part of its defense against pathogens. In this review, we examine how the respiratory epithelium senses and responds...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2018-0247TR
更新日期:2019-03-01 00:00:00
abstract::Glucose moves into airway secretions after a glucose load. Therefore people with diabetes or hyperglycemia spend a significant proportion of each day with glucose in their airways secretions. This study investigated the effects of glucose on isolated human airways and on cultured airway smooth muscle (ASM) cells. Huma...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2011-0449OC
更新日期:2012-10-01 00:00:00
abstract::Mutations in the p53 gene have been implicated to play an important role in the development of various human cancers. To evaluate the importance of p53 in lung cancer, a transgenic mouse model was established by utilizing the Clara cell secretory protein (CCSP) promoter to target the expression of a dominant-negative ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.27.2.4799
更新日期:2002-08-01 00:00:00
abstract::Platelet-activating factor (PAF), a proinflammatory lipid mediator, is a potent airway mucin secretagogue. This study assessed the role of protein kinase C (PKC) in PAF-induced mucin release from primary cultures of feline tracheal epithelial cells (FTEC). Mucin secretion was quantitated by enzyme-linked immunosorbent...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.11.2.8049080
更新日期:1994-08-01 00:00:00
abstract::Patients with acute lung injury or respiratory distress syndrome often require supplemental oxygen to maintain tissue oxygenation; however, this treatment can cause or worsen lung inflammation. CD44 is a transmembrane adhesion molecule that is present on a wide variety of cell types, including leukocytes and parenchym...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0158OC
更新日期:2011-03-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is a key enzyme involved in the inflammatory process that is rapidly induced in macrophages in response to LPS. Carbon monoxide (CO), a byproduct of heme oxygnease-1, can suppress proinflammatory response in various in vitro and in vivo models of inflammation. This study was undertaken to exam...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0154OC
更新日期:2006-08-01 00:00:00
abstract::Smoking cigarettes is the major risk factor for chronic obstructive pulmonary disease (COPD). COPD is a condition associated with chronic pulmonary inflammation, characterized by macrophage activation, neutrophil recruitment, and cell injury. Many substances contained in cigarette smoke, including reactive oxygen spec...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0130OC
更新日期:2007-11-01 00:00:00
abstract::Na(+) absorption and Cl(-) secretion are in equilibrium to maintain an appropriate airway surface fluid volume and ensure appropriate mucociliary clearance. In cystic fibrosis, this equilibrium is disrupted by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in the absence of ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0456OC
更新日期:2009-02-01 00:00:00
abstract::The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-H...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0111OC
更新日期:2017-01-01 00:00:00
abstract::Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mec...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2011-0273OC
更新日期:2013-05-01 00:00:00
abstract::Isoprostanes are prostaglandin-like molecules that accumulate in oxidative stress and also exert powerful biological effects on a wide variety of tissues. We investigated the effects of several different isoprostanes on contractions evoked by electrical field stimulation (EFS) in bovine trachealis, finding only 15-E2t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0022OC
更新日期:2007-12-01 00:00:00
abstract::The capacity of Mycobacterium tuberculosis (MTB) to induce production of chemokines with known chemotactic activity for monocytes and lymphocytes, the cellular building blocks of granulomas, was investigated. These chemokines included regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte c...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.3.2815
更新日期:1998-09-01 00:00:00
abstract::Hydrogen sulfide (H2S), a novel signaling gasotransmitter in the respiratory system, may have antiinflammatory properties in the lung. We examined the preventive and therapeutic effects of H2S on ozone-induced features of lung inflammation and emphysema. C57/BL6 mice were exposed to ozone or filtered air over 6 weeks....
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2015-0014OC
更新日期:2016-07-01 00:00:00
abstract::We recently described overproduction of interferon (IFN)-gamma by lung lymphocytes in mice with silicosis (11% of cells in air-control versus 19% of cells from silica-exposed mice; Davis and colleagues, Am. J. Respir. Cell Mol. Biol. 1999;20:813-824). We hypothesized that the increased IFN-gamma production might be du...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.22.4.3599
更新日期:2000-04-01 00:00:00
abstract::Inflammatory lung diseases are associated with increased production of matrix metalloproteinase-9 (MMP-9) from infiltrating granulocytes or from the respiratory epithelium, and inappropriate expression and activation of MMP-9 may be associated with tissue injury and airway remodeling. Inflammatory conditions also resu...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0039OC
更新日期:2002-10-01 00:00:00
abstract::The cystic fibrosis transmembrane conductance regulator (CFTR) serves a pivotal role in normal epithelial homeostasis; its absence leads to destruction of exocrine tissues, including those of the gastrointestinal tract and lung. Acute regulation of CFTR protein in response to environmental stimuli occurs at several le...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0452OC
更新日期:2008-11-01 00:00:00
abstract::It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been demonstrated in the ai...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.24.6.4217
更新日期:2001-06-01 00:00:00
abstract::Higher numbers of eosinophil/basophil colony-forming units (Eo/B CFU) are observed in blood of atopic individuals, and can be enhanced in atopic asthmatics by allergen-inhalation challenge. It is known that mature basophils and eosinophils synthesize cytokines relevant to allergic inflammation. To investigate the pote...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.1.2871
更新日期:1998-07-01 00:00:00
abstract::We have previously observed that mice exposed to cigarette smoke and treated with exogenous alpha(1)-antitrypsin (A1AT) were protected against the development of emphysema and against smoke-induced increases in serum TNF-alpha. To investigate possible mechanisms behind this latter observation, we cultured alveolar mac...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0345OC
更新日期:2007-08-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a major disease of the lungs. It primarily occurs after a prolonged period of cigarette smoking. Chronic inflammation of airways and the alveolar space as well as lung tissue destruction are the hallmarks of COPD. Recently it has been shown that cellular senescence might...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2013-0382PS
更新日期:2014-09-01 00:00:00
abstract::Proteinase-activated receptor (PAR)-2 is cleaved within its aminoterminal extracellular domain by serine proteinases such as trypsin, unmasking a new aminoterminus starting with the sequence SLIGKV, which binds intramolecularly and activates the receptor. PAR-2 has been reported to be involved in inflammation within t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.4908
更新日期:2003-03-01 00:00:00
abstract::Chronic hypoxia induces proliferation of human pulmonary artery smooth muscle cells (hPASMCs), leading to remodeling and pulmonary hypertension, but the mechanism remains unclear. The present study tested the roles of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) and mitochondrial membrane potential (Delt...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2009-0017OC
更新日期:2010-06-01 00:00:00