Muzeyyen Izmirli

The cell fate: senescence or quiescence

Senescence and quiescence are frequently used as interchangeable terms in the literature unwittingly. Despite the fact that common molecules play role in decision of cell cycle arrest, senescent and quiescent cells have some distinctive phenotypes at both molecular and morphological levels. Thus, in this review we summarized the features of senescence and quiescence with respect to visual characteristics and prominent key molecules. A PubMed research was conducted for the key words; “senescence”, “quiescence” and “cell cycle arrest”. The results which are related to cell cycle control were selected. The selection criteria of the target articles used for this review included also key cell cycle molecules such as p53, pRB, p21, p16, mTOR, p27, etc. The results were not evaluated statistically. The mechanistic target of rapamycin (mTOR) has been claimed to be key molecule in switching on/off senescence/quiescence. Specifically, although maximal p53 activation blocks mTOR and causes quiescence, partial p53 activation sustains mTOR activity and causes senescence subsequently. In broader perspective, quiescence occurs due to lack of nutrition and growth factors whereas senescence takes place due to aging and serious DNA damages. Contrary to quiescence, senescence is a degenerative process ensuing a certain cell death. We highlighted several differences between senescence and quiescence and their key molecules in this review. Whereas quiescence (cell cycle arrest) is only one half of the senescence, the other half is growth stimulation which causes actual senescence phenotype.

Do fasudil and Y-27632 affect the level of transient receptor potential (TRP) gene expressions in breast cancer cell lines?

Breast cancer (BC) is the most frequent cancer type in women, and the mortality rate is high especially in metastatic disease. Ion channels such as the transient receptor potential (TRP) channels correlate with malignant growth and cancer progression. Hence, some authors have suggested that the expression levels of TRP channels may be used as a marker in the diagnosis and predicting the prognosis of BC. Also, in some recent studies, targeting TRP channels are suggested as a novel treatment strategy in BC. The aim of this study was to investigate the effect of two Rho-kinase (ROCK) inhibitors, fasudil and Y-27632, on the expression levels of TRP channel genes in breast cancer cell lines (ZR-75-1, MCF7, and MDA-MB-231) and breast epithelial cell line (hTERT-HME1). The expression levels of TRP genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that fasudil had reduced the TRPC1, TRPV2 expression levels in the ZR-75-1, MCF7, and MDA-MB-231 cell lines. On the other hand, fasudil and Y-27632 had reduced TRPM6 expression levels in all cell lines. Y-27632 increased the expression levels of TRPC7 in all cell lines. In conclusion, this is the first study demonstrating that the inhibition of ROCK pathway changes the expression levels of some TRP genes. Also, our study has firstly shown that the expression levels of the TRP genes which are suggested as a diagnostic and prognostic biomarker in BC, were changed with the treatment of fasudil and Y-27632.

The spectrum of β-thalassemia mutations in Hatay, Turkey: reporting three new mutations.

Abstract β-Thalassemia (β-thal) is an important health problem in Hatay, Southern Turkey, because of its high carrier frequency and the frequency of consanguinity. The aim of this study was to reveal the spectrum of β-thal mutations and to provide a foundation for prenatal genetic testing that will be a part of an effective prevention program for β-thal disease in Hatay. We determined the spectrum of β-thal mutations in 93 unrelated affected patients. Using a direct sequencing method, we identified a large number of β-thal mutations. We found different results from other parts of Turkey. A total of 16 different β-thal mutations were characterized in the parents. The most common mutations were: IVS-I-110 (G>A), IVS-I-6 (T>C), IVS-I-1 (G>A), frameshift codon (FSC) 8 (–AA), codon 39 (C>T) and IVS-II-745 (C>G). Since our region has seen many Syrian and Iraqi immigrants, we report that the prevalence of the thalassemia traits are different from other regions of Turkey. Our study demonstrates the spectrum of β-thal mutations in the Hatay region, and that there was great molecular heterogeneity.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in psoriasis in southern Turkey.

Background Psoriasis is a multigenic and multifactorial dermatological disease linked to cardiovascular diseases. Increased levels of homocysteine in patients with psoriasis have been demonstrated in many studies. The most frequently investigated genetic defect that plays a role in homocysteine metabolism is single point substitution (C to T) located on the 677th nucleotide of the methylenetetrahydrofolate reductase gene (MTHFR). Objective In this study, we aimed to investigate methylenetetrahydrofolate C677T polymorphism in psoriasis patients in Turkey. Methods The study included 96 patients with psoriasis and 77 controls from southern Turkey. Methylenetetrahydrofolate C677T polymorphism was analysed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism methods. Results In the psoriasis group, 34 CC (35.4%), 46 CT (47.9%) and 16 TT (16.7%) genotypes were found, respectively; while in the control group, the figures were 39 (50.6%), 35 (45.5%), 3 (3.9%). Homozygote and heterozygote T alleles of methylenetetrahydrofolate C677T polymorphism were significantly higher in the psoriasis than in the control group (p=0.013). Conclusion We firstly found a correlation between methylenetetrahydrofolate C677T polymorphism and psoriasis among the southern Turkish population.

HATAY İLİ’NDE MTHFR C677T TEK NÜKLEOTİT POLİMORFİZMİ VE PROSTAT KANSERİ ARASINDAKİ İLİŞKİNİN DEĞERLENDİRİLMESİ

MTHFR (Methylenetatrahydrofolate reductase) is one of the most important enzymes because of its function about folate metabolism and DNA synthesis nucleotide polymorphism in the gene encoding the enzyme, have been associated with many diseases including prostate cancer. We aimed to evaluate the association between the polymorphism and prostate cancer by comparing the results between patients and controls

Investigation of p53 Tumor Suppressor Gene Mutations in Patients with a Lung Mass Using Sequence Analysis

ABS TRACT Ob jec ti ve: The p53 tu mo ur sup pres sor ge ne plays an im por tant ro le in the re gu la ti on of cell pro li fe ra ti on. It is lo ca ted on the short arm of the 17th chro mo so me. It has 11 exons and en co des for a tu mor sup pres sor pro te in cal led p53 which is 53kD in we ight and 393 ami no acids in length. This pro te in, a trans crip ti on fac tor, is an im por tant re gu la tor of cell cycle. Up to da te, a num ber of mu ta ti ons (75 % of which are fo und bet we en co don 26 and 332) ha ve be en de tec ted on p53 ge ne. Recent re se arc hes sho wed that lung ne op lasm re sul ting from the mu ta ti ons of p53 ge ne va ri ed bet we en 33% (ade no car ci no ma) and 70% (small cell lung can cer), and it is re por ted that the hot spots were ma inly fo und at the co dons 175, 248, and 273. Ma te ri al and Met hods: In this study, the exons, exonin tron junc ti ons, and so me in tron re gi ons, which are lo ca ted bet we en exon 4-9 of p53 ge ne, of 24 pati ents who had a sur gi cal ope ra ti on du e to a lung mass we re exa mi ned by au to ma tic DNA se qu en cing in Uni ver sity of Le ip zig. Re sults: 53 mis sen se and 7 fra mes hift mu ta ti ons we re de tec ted bet we en 4th and 9th exons (Co dons 36-318) of 18 samp les among the 24 samp les. Fifty five of the se mu ta ti ons we re he te rozy go us, and five of them were ho mozy go us. Si mi larly, 12 mis sen se mu ta ti ons de tec ted as a re sult of the se ri al analy ses of the re gi on bet we en in trons 4-9, and seven of them we re he te rozy go us and 5 we re ho mozy go us. Conc lu si on: So me re se arch re gar ding p53 ge ne re por ted that co don 175, 248, and 273 were hot spots and mu ta ti ons were fre qu ent in the se co dons. Ho we ver we ha ve not se en any mu ta ti ons in any of the se co dons in our study. Nuc le o ti de chan ges at the po si ti ons 13432 (5’ be gin ning) and 13999 (3’ en ding) of 6th in tron, which are very im por tant re gi ons, may re sult in the for ma ti on of an ab nor mal pro te in. We sup po se that ot her nuc le o ti de chan ges are not very im por tant du e to the ir he te rozy go us na tu re and lo ca ti on.