The influence of peptides from the angiotensin family on tyrosine kinase activity and cell viability in a human hormone-dependent prostate cancer line

Wstęp: Wyniki wielu badań wskazują, że peptydy z rodziny angiotensyn są włączone w regulację cyklu komórkowego, apoptozę, różnicowanie się komórek, jak również odgrywają istotną rolę w procesach zapalnych i migracji komórek. Ich zaangażowanie w tak istotne procesy sugeruje, że mogą one odgrywać istotną rolę w procesie kancerogenezy. Stosunkowo mało wiadomo na temat roli systemu renina-angiotensyna w zapoczątkowaniu i późniejszym rozwoju raka stercza. Materiał i metody: Poniższe wyniki przedstawiają wpływ Ang II, Ang III, Ang IV na linię komórkową ludzkiego hormonozależnego raka prostaty. Używając metody izotopowej, badano wpływ wybranych angiotensyn na aktywność kinaz tyrozynowych. Podczas gdy przeżywalność komórkowa była oznaczana za pomocą testu MTT. Wyniki: Wyniki wskazują, że tylko Ang IV w sposób istotny statystycznie redukuje aktywność kinaz tyrozynowych i obniża przeżywalność komórek linii LNCaP. Proces ten był pośredniczony przez receptor AT2 i prawdopodobnie przez inny receptor, o wysokim powinowactwie dla Ang IV i niskim dla PD123319 i losartanu. Wnioski: Otrzymane wyniki sugerują, że komponenty układu renina–angiotensyna, w tym szczególnie peptydy angiotensynowe oraz klasyczne receptory dla angiotensyn (AT1, AT2), mogą modyfikować przeżywalność komórek raka gruczołu krokowego.Introduction: The results of many studies have reported that peptides from the angiotensin family are involved in the regulation of cell growth, proliferation, cell migration, apoptosis, inflammation, differentiation, and angiogenesis, which suggests that they might play an important role in carcinogenesis. The role of the renin–angiotensin system in supporting prostate cancer induction and progression has so far received little study. Material and methods: The present study was to examine the influence of Ang II, Ang III, and Ang IV on a human hormone-dependent prostate cancer line (LNCaP). Using an isotopic method, we tested the effects of angiotensins on tyrosine kinase activity, and measured cell viability using an MTT Assay. Results: The results showed that only Ang IV significantly reduced tyrosine kinase activity and cell viability in LNCaP cells. The process seemed to be mediated partly by AT2 and probably by another type of receptor with high affinity for Ang IV and low affinity for PD123319 and Losartan. Conclusions: These findings suggest that components of the renin-angiotensin system, specifically angiotensin peptides and receptors (AT1, AT2) can modify prostate cancer cell viability

Influence of myocardial infarction on changes in the expression of angiotensin type 1 receptor in the rat prostate

Angiotensin II (AngII) is the biologically active peptide of the renin-angiotensin system (RAS). Tissue- based, local RAS has been identified in the prostate, testis, epididymis and coagulating glands. Experimental and clinical studies have consistently shown that myocardial infarction (MI) is associated with activation of the systemic RAS with increased concentration of angiotensin peptides in the blood and changes in expression of angiotensin receptors (AT). Changes in angiotensin receptors in the renal and cardiovascular system after MI are well recognized, but the effects of MI influence on changes in other tissue like the prostate gland are unknown. In the present study, we investigated the effect of myocardial infarction on angiotensin receptor protein and mRNA expression in the rat prostate gland. MI model was established in Wistar rats by ligating the left coronary artery (modified Selye method). The levels of AT1a-b and AT2 receptor mRNAs and proteins were measured in the rat prostate. Our study demonstrates tissue-specific changes in AT1a-b and AT2 receptor expression after myocardial infarction. The results show that MI has a strong influence on the expression of angiotensin receptor type AT1 in the prostate at the protein and mRNA level. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 3, 497–503

Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin

This study was undertaken to verify whether simvastatin modulates Cav-1/eNOS expression, and if this modulation is associated with changes in pro- and anti-inflammatory cytokine and Toll-like receptor 4 (TLR4) level in abdominal aortic aneurysm (AAA). It is a 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment decreased Cav-1 (p0.05) and increased IL-10 concentration (p=0.055); however, TLR4 expression was unaffected, suggesting that simvastatin influences Cav-1 and eNOS in the AAA wall by other mechanisms. Simvastatin may modulate Cav-1 and eNOS expression in the aneurysmal wall, indicating a potentially beneficial role for statins in AAA patients

Development of culture and cultural institutions in Nowa Huta in the era of socialism and after the turn of the political system in 1989

Niniejsza praca opisuje rozwój kultury i instytucji kultury Nowej Hucie, zarówno w dobie socjalizmu jak i po przełomie ustrojowym, który miał miejsce w 1989 roku. Przedstawiona została historia dzielnicy, specyfika nowohuckiej społeczności, a przede wszystkim to w jaki sposób kształtowały się tam instytucje i inicjatywy kulturalne. Praca ta ma na celu ukazanie w jaki sposób współczesne instytucje kultury bazują na historii i dorobku Nowej Huty oraz przedstawienie jej jako miejsca ciekawego i atrakcyjnego mimo nękających ją stereotypów.This paper describes the development of culture and cultural institutions in Nowa Huta, both in the era of socialism and after the turn of the political system, which took place in 1989. Presented in the paper history of the district, the nature of society in Nowa Huta, and most of all is institutions and cultural initiatives develops out there. This work aims to show how the modern cultural institutions are based on the history and heritage of Nowa Huta and to present it as an interesting and attractive place despite of adverse stereotypes

Cell Cycle Status Influences Resistance to Apoptosis Induced by Oxidative Stress in Human Breast Cancer Cells, Which Is Accompanied by Modulation of Autophagy

Cancer cells are characterised by uncontrolled cell proliferation; however, some of them can temporarily arrest their cell cycle at the G0 or G1 phase, which could contribute to tumour heterogeneity and drug resistance. The cell cycle status plays a critical role in chemosensitivity; however, the influence of G0- and G1-arrest has not been elucidated. To study the cell cycle arrest-mediated resistance, we used MCF-7 cells and generated three populations of cells: (1) cells arrested in the G0-like phase, (2) cells that resumed the cell cycle after the G0-like phase and (3) cells arrested in early G1 with a history of G0-like arrest. We observed that both the G0-like- and the G1-arrested cells acquired resistance to apoptosis induced by oxidative stress, accompanied by a decreased intracellular reactive oxygen species and DNA damage. This effect was associated with increased autophagy, likely facilitating their survival at DNA damage insult. The cell cycle reinitiation restored a sensitivity to oxidative stress typical for cells with a non-modulated cell cycle, with a concomitant decrease in autophagy. Our results support the need for further research on the resistance of G0- and G1-arrested cancer cells to DNA-damaging agents and present autophagy as a candidate for targeting in anticancer treatment

Coexpression of CAV-1, AT1-R and FOXM1 in prostate and breast cancer and normal cell lines and their influence on metastatic properties

The aim of this study was to evaluate the coexpression of caveolin-1 (CAV-1), angiotensin II type 1 receptor (AT1-R) and forkhead box Ml (FOXM1) in prostate and breast cancer cell lines, in comparison with normal cell lines. CAV-1, AT1-R and FOXM1 expression was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis in the prostate cancer cell lines PC3, DU145 and LNCaP; prostate normal cell line PNT1A; breast cancer cell lines MCF-7 and MDA-MB-231; and the normal breast cell line 184A1. A correlation between the expression levels of the investigated genes and their metastatic properties was determined by the Spearman's rank test (P<0.05) and Aspin-Welsch t-test, respectively. In prostate cell lines, a significant correlation was noted between CAV-1 and AT1-R expression and between FOXM1 and CAV-1 expression. A correlation between the expression levels of the investigated genes and their metastatic potential was also observed, with relatively high expression of all the investigated genes in the normal prostate cell line PNT1A. In comparison to prostate cancer cell lines, an adverse dependency between CAV-1, AT1-R, FOXM1 expression and metastatic potential was observed in the breast cancer cell lines. Relatively high expression of all tested genes was observed in the normal breast cell line 184A1, which was decreasing respectively with increasing metastatic potential of breast cancer cell lines. The results obtained here indicate that CAV-1, FOXM1 and AT1-R may be potential markers of tumorigenesis in certain types of cancer in vitro

Intestinal Barrier, Claudins and Mycotoxins

The intestinal barrier is the main barrier against all of the substances that enter the body. Proper functioning of this barrier guarantees maintained balance in the organism. Mycotoxins are toxic, secondary fungi metabolites, that have a negative impact both on human and animal health. It was postulated that various mycotoxins may affect homeostasis by disturbing the intestinal barrier. Claudins are proteins that are involved in creating tight junctions between epithelial cells. A growing body of evidence underlines their role in molecular response to mycotoxin-induced cytotoxicity. This review summarizes the information connected with claudins, their association with an intestinal barrier, physiological conditions in general, and with gastrointestinal cancers. Moreover, this review also includes information about the changes in claudin expression upon exposition to various mycotoxins