Developmental expression and localization of the catalytic subunit of protein phosphatase 2A in rat lung

Cheng, Xue; Heller, Felice; Johns, Roger A.

doi:10.1002/(sici)1097-0177(199801)211:1<1::aid-aja1>3.0.co;2-l

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…We have demonstrated previously that PP2A is broadly expressed during early lung development, becoming localized later predominantly in the earliest developing epithelium and endothelium as the lung matures (37). Because the role of PP2A in mammalian organogenesis remains largely unexplored, the present study demonstrates that PP2A has a significant role in the regulation of lung growth, regulating the cell cycle of mesenchymal cells and differentiation of the respiratory epithelium.…”

supporting

confidence: 55%

“…In the lung, PP2A and PP1 activities are developmentally regulated in whole lung homogenates peaking after birth (31). PP2A expression is also developmentally regulated, being broadly expressed by both epithelial and mesenchymal cells in the early fetal 14-to 17-day rat lung (37). By 19 days, expression predominates in the earliest forming airways with diminished expression at this stage in the mesenchyme or in the more differentiated bronchial epithelium (37).…”

Section: Discussionmentioning

confidence: 99%

“…PP2A expression is also developmentally regulated, being broadly expressed by both epithelial and mesenchymal cells in the early fetal 14-to 17-day rat lung (37). By 19 days, expression predominates in the earliest forming airways with diminished expression at this stage in the mesenchyme or in the more differentiated bronchial epithelium (37). Because PP2A is likely to have many substrates in the developing lung and could therefore regulate many developmental processes, the role of PP2A, if any, in regulating lung development was unclear.…”

Section: Discussionmentioning

confidence: 99%

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Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures

Taylor

Stoops

Everett

2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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Protein phosphatase 2A (PP2A) is a key signal transduction intermediate in the regulation of cellular proliferation and differentiation in vitro. However, the role of PP2A in the context of a developing organ is unknown. To explore the role of PP2A in the regulation of lung development, we studied the effect of PP2A inhibition on new airway branching, induction of apoptosis, DNA synthesis, and expression of epithelial marker genes in whole organ explant cultures of embryonic (E14) rat lung. Microdissected lung primordia were cultured in medium containing one of either two PP2A inhibitors, okadaic acid (OA, 0-9 nM) or cantharidin (Can, 0-3,600 nM), or with the PP2B inhibitor deltamethrin (Del, 0-10 microM) as a control for a PP2A-specific effect for 48 h. PP2A inhibition with OA and Can significantly inhibited airway branching and overall lung growth. PP2B inhibition with Del did not affect lung growth or new airway development. Histologically, both PP2A- and PP2B-inhibited explants were similar to controls. Increased apoptosis was not the mechanism of decreased lung growth and new airway branching inasmuch as OA-treated explant sections subjected to the terminal deoxynucleotidyltransferase dUTP nick end labeling reaction demonstrated a decrease in apoptosis. However, PP2A inhibition with OA increased DNA content and 5-bromo-2'-deoxyuridine uptake that correlated with a G(2)/M cell cycle arrest. PP2A inhibition also resulted in altered differentiation of the respiratory epithelium as evidenced by decreased mRNA levels of the early epithelial marker surfactant protein C. These findings suggest that inhibition of protein phosphatases with OA and Can halted mesenchymal cell cycle progression and reduced branching morphogenesis in fetal rat lung explant culture.

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supporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures

Taylor

Stoops

Everett

2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…These results indicated that PP2Ac is expressed ubiquitously, not only in reactive alveolar epithelium, but also in lung adenocarcinoma cells, since PP2A is an important and universal regulator of numerous target proteins within the diverse signaling pathways that underlie cell growth and proliferation, apoptosis, DNA replication, transcription and translation. 26 Furthermore, PP2Ac is highly expressed in the embryonic lung of the unborn rat, 33 and it is possible to consider that PP2Ac expression is secondarily related to tissue regeneration, high growth ability and the cell cycle. In fact, in comparison to normal type 2 pneumocytes, reactive type 2 pneumocytes in organized pneumonia showed a high labeling index for Ki-67 protein, similarly to AAH.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of immunoglobulin (CD79a) binding protein1 (IGBP‐1) in small lung adenocarcinomas and its clinicopathological significance

Sakashita¹,

Li²,

Nashima³

et al. 2011

Pathology International

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Immunoglobulin binding protein 1 (IGBP-1) was initially identified as a signal transduction molecule coprecipitating with MB1 (Igα) of the B cell antigen receptor (BCR) complex and was later found to be broadly expressed. Immunoglobulin binding protein 1 has been characterized as an associated and regulatory component of the catalytic subunits of protein phosphatase 2A (PP2A), which is the most abundant phosphatase and plays important roles in cell growth and cell cycle control. The aim of this study was to investigate the expressional characteristics of IGBP-1 and PP2Ac during pulmonary adenocarcinogenesis. The positivity rate of IGBP-1 increased during the course of sequential progression from non-invasive carcinoma (8/30, 26.7%) to invasive adenocarcinoma (37/46, 80.4%) among cases that showed areas of lepidic growth. In contrast, all of the small adenocarcinomas showing a non-lepidic growth pattern were positive for IGBP-1 (20/20, 100%). All cancers that proved ultimately fatal were positive for IGBP-1, and log-rank analysis showed that IGBP-1 positivity was significantly correlated with a poor prognosis. In contrast, atypical adenomatous hyperplasias and lung adenocarcinomas were uniformly positive for PP2Ac. Protein phosphatase 2A was not associated with carcinoma progression. Thus we have demonstrated that IGBP-1 is expressed universally in advanced lung adenocarcinomas, and that its overexpression is significantly related to outcome.

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“…No lung lesions following repeated intranasal administration were reported by Fitzgeorge et al (1994), despite the fact that a portion of an intranasally administered dose to anesthetized rodents reaches the lung (Balmelli et al, 1998). Protein phosphatase 2 plays a major role in lung development (Taylor et al, 2000;Xue et al, 1998), but no documentation of this enzyme in adult lung tissue could be found in the literature. The NOAEL for the nasal lesions occurred at an estimated deposited dose of 3 μg microcystin/kg/day, occurring after exposure to approximately 260 μg microcystin/m 3 for 0.5 h/day.…”

Section: Discussionmentioning

confidence: 99%

The toxicity of microcystin LR in mice following 7 days of inhalation exposure

Benson

Hutt

Rein

et al. 2005

Toxicon

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Microcystins, a family of cyclic heptapeptides produced by the cyanobacteria, Microcystis aeruginosa, have documented hepatotoxic and tumor promoting activities. The purpose of this study was to evaluate the toxicity of inhaled microcystin LR (microcystin). Male BALB/c mice were exposed by nose-only inhalation to 260-265 μg microcystin/m 3 for 7 days. The low-, mid-and highdose groups were exposed for 0.5, 1, and 2 h, respectively. Control animals were sham exposed to aerosolized vehicle. Treatment-related microscopic lesions were observed only in the nasal cavity of the mid-and high-dose groups. These lesions consisted of minimal to moderate multifocal degeneration and necrosis of the respiratory epithelium, with variable neutrophilic inflammation and minimal to marked degeneration, necrosis, and atrophy of the olfactory epithelium. The no-adverseeffect dose for the nasal lesions was approximately 3 μg/kg body weight, or 20 ng/cm 2 of nasal epithelium. In serum, only two protein peaks, occurring at m/zs of 11,688 and 11,829 Da, exhibited decreases in intensity that were microcystin dose-dependent. While these proteins have not been positively identified, they may be useful in the future as biomarkers of microcystin exposure in humans.

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Developmental expression and localization of the catalytic subunit of protein phosphatase 2A in rat lung

Cited by 10 publications

References 31 publications

Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures

Protein phosphatase inhibitors arrest cell cycle and reduce branching morphogenesis in fetal rat lung cultures

Overexpression of immunoglobulin (CD79a) binding protein1 (IGBP‐1) in small lung adenocarcinomas and its clinicopathological significance

The toxicity of microcystin LR in mice following 7 days of inhalation exposure

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