scholarly journals Proteomic analysis of oxymatrine-induced changes in lung fibroblasts

2012 ◽  
Vol 6 (45) ◽  
pp. 3136-3144
Author(s):  
Xiao-Hong Chen
Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1164
Author(s):  
Siying Song ◽  
Linlin Guo ◽  
Di Wu ◽  
Jingfei Shi ◽  
Yunxia Duan ◽  
...  

Background: Animal and clinical studies have shown that remote ischemic conditioning (RIC) has protective effects for cerebral vascular diseases, with induced humoral factor changes in the peripheral blood. However, many findings are heterogeneous, perhaps due to differences in the RIC intervention schemes, enrolled populations, and sample times. This study aimed to examine the RIC-induced changes in the plasma proteome using rhesus monkey models of strokes. Methods: Two adult rhesus monkeys with autologous blood clot-induced middle cerebral artery (MCA) occlusion underwent RIC interventions twice a week for five consecutive weeks. Each RIC treatment included five cycles of five minutes of ischemia alternating with five minutes of reperfusion of the forearm. The blood samples were taken from the median cubital vein of the monkeys at baseline and immediately after each week’s RIC stimulus. The plasma samples were isolated for a proteomic analysis using mass spectrometry (MS). Results: Several proteins related to lipid metabolism (Apolipoprotein A-II and Apolipoprotein C-II), coagulation (Fibrinogen alpha chain and serpin), immunoinflammatory responses (complement C3 and C1), and endovascular hemostasis (basement membrane-specific heparan sulfate proteoglycan) were significantly modulated after the RIC intervention. Many of these induced changes, such as in the lipid metabolism regulation and anticoagulation responses, starting as early as two weeks following the RIC intervention. The complementary activation and protection of the endovascular cells occurred more than three weeks postintervention. Conclusions: Multiple protective effects were induced by RIC and involved lipid metabolism regulation (anti-atherogenesis), anticoagulation (antithrombosis), complement activation, and endovascular homeostasis (anti-inflammation). In conclusion, this study indicates that RIC results in significant modulations of the plasma proteome. It also provides ideas for future research and screening targets.


2008 ◽  
Vol 169 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Xiaoping Ao ◽  
David M. Lubman ◽  
Mary A. Davis ◽  
Xianying Xing ◽  
Feng-Ming Kong ◽  
...  

2020 ◽  
Author(s):  
Ashani Weeraratna ◽  
Mitchell Fane ◽  
Stephen Douglass ◽  
Gretchen Alicea ◽  
Marie Webster ◽  
...  

Abstract Dormant tumor cells escape the primary site, do not grow out into macroscopic tumors in the distal site, but maintain enough plasticity to reactivate and form overt metastatic lesions, sometimes taking several decades. Despite its importance in metastasis and residual disease, few studies have been able to successfully model or characterize dormancy within melanoma. Here, we show that age-related changes in the lung microenvironment facilitate a permissive niche for efficient outgrowth of disseminated dormant tumor cells, in contrast to the aged skin, where age-related changes suppress melanoma growth but drive dissemination. A model of melanoma progression that addresses these microenvironmental complexities is the phenotype switching model, which argues that melanoma cells switch between a proliferative cell state and a slower-cycling, invasive state1–3. Dermal fibroblasts are key orchestrators of promoting phenotype switching in melanoma via changes in the secretion of soluble factors during aging4–8. Specifically, we have identified Wnt5A as a master regulator of activating metastatic dormancy, which enables efficient seeding and survival of melanoma cells in metastatic niches. Age-induced reprogramming of lung fibroblasts increases their secretion of the soluble Wnt antagonist sFRP1, which inhibits Wnt5A, enabling efficient metastatic outgrowth. Further, we have identified the tyrosine kinase receptors AXL and MER as promoting a dormancy-to-reactivation axis respectively. Overall, we find that age-induced changes in distal metastatic microenvironments promotes efficient reactivation of dormant melanoma cells in the lung.


2010 ◽  
Vol 78 (2) ◽  
pp. 547-554 ◽  
Author(s):  
Vasily A. Yakovlev ◽  
Christopher S. Rabender ◽  
Heidi Sankala ◽  
Ben Gauter-Fleckenstein ◽  
Katharina Fleckenstein ◽  
...  

2006 ◽  
Vol 5 (10) ◽  
pp. 2656-2665 ◽  
Author(s):  
G. E. Kisby ◽  
M. Standley ◽  
T. Park ◽  
A. Olivas ◽  
S. Fei ◽  
...  

2017 ◽  
Vol 15 (6) ◽  
pp. 339-351 ◽  
Author(s):  
Mandar Dave ◽  
Abul B.M.M.K. Islam ◽  
Roderick V. Jensen ◽  
Agueda Rostagno ◽  
Jorge Ghiso ◽  
...  

2017 ◽  
Vol 312 (6) ◽  
pp. L945-L958 ◽  
Author(s):  
Anne E. Wyman ◽  
Zahid Noor ◽  
Rita Fishelevich ◽  
Virginia Lockatell ◽  
Nirav G. Shah ◽  
...  

Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. A better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, SIRT3, and SIRT6, are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls. These unbiased tests revealed a tendency for all sirtuins to be expressed at lower levels in fibroblasts from patients compared with controls, but the greatest decrease was observed with SIRT7. Similarly, SIRT7 was decreased in lung tissues of bleomycin-challenged mice. Inhibition of SIRT7 with siRNA in cultured lung fibroblasts resulted in an increase in collagen and α-smooth muscle actin (α-SMA). Reciprocally, overexpression of SIRT7 resulted in lower basal and TGF-β-induced levels of COL1A1, COL1A2, COL3A1, and α-SMA mRNAs, as well as collagen and α-SMA proteins. Induced changes in SIRT7 had no effect on endogenous TGF-β mRNA levels or latent TGF-β activation, but overexpression of SIRT7 reduced the levels of Smad3 mRNA and protein. In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.


2002 ◽  
Vol 282 (2) ◽  
pp. L185-L192 ◽  
Author(s):  
Claudette M. St. Croix ◽  
K. J. Wasserloos ◽  
K. E. Dineley ◽  
I. J. Reynolds ◽  
E. S. Levitan ◽  
...  

We hypothesized that metallothionein (MT), a cysteine-rich protein with a strong affinity for Zn2+, plays a role in nitric oxide (NO) signaling events via sequestration or release of Zn2+ by the unique thiolate clusters of the protein. Exposing mouse lung fibroblasts (MLF) to the NO donor S-nitrosocysteine resulted in 20–30% increases in fluorescence of the Zn2+-specific fluorophore Zinquin that were rapidly reversed by the Zn2+ chelator N,N,N′, N′-tetrakis-(2-pyridylmethyl)ethylenediamine. The absence of a NO-mediated increase in labile Zn2+ in MLF from MT knockouts and its restoration after MT complementation by adenoviral gene transfer inferred a critical role for MT in the regulation of Zn2+ homeostasis by NO. Additional data obtained in sheep pulmonary artery endothelial cells suggested a role for the apo form of MT, thionein (T), as a Zn2+-binding protein in intact cells, as overexpression of MT caused inhibition of NO-induced changes in labile Zn2+ that were reversed by Zn2+ supplementation. Furthermore, fluorescence-resonance energy-transfer data showed that overexpression of green fluorescent protein-modified MT prevented NO-induced conformational changes, which are indicative of Zn2+ release from thiolate clusters. This effect was restored by Zn2+ supplementation. Collectively, these data show that MT mediates NO-induced changes in intracellular Zn2+ and suggest that the ratio of MT to T can regulate Zn2+ homeostasis in response to nitrosative stress.


PROTEOMICS ◽  
2010 ◽  
Vol 10 (1) ◽  
pp. 99-114 ◽  
Author(s):  
Elke Hammer ◽  
Sandra Bien ◽  
Manuela Gesell Salazar ◽  
Leif Steil ◽  
Christian Scharf ◽  
...  

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