Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

The present study\u27s objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with IC50 values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L–1. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (p < 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (p < 0.001), which leads the cells to trigger apoptosis. In conclusion, the present in vitro study may supply a significant background for in vivo studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify

Nöroblastoma Hücre Hattında Uzun Süreli Darbeli Elektromanyetik Alan Maruziyetinin Apoptoz Üzerine Etkileri

Darbeli Elektromanyetik Alan (PEMF) düşük frekanslı elektromanyetik alan olup son yıllarda klinik araştırmalarda tedavi amaçlı uygulanmasına yönelik çalışmalar hız kazanmıştır. Farklı frekans, yoğunluk, dalga boyu ve sürelerde kematerapötik ilaçlarla birlikte uygulanan PEMF maruziyetinin beyin kanseri hücreleri dahil çeşitli kanser hücrelerinde apoptoz üzerine etkilerini değerlendiren çalışmalardan farklı olarak çalışmada sabit frekans ve yoğunlukta (50 Hz, 1 mT) uzun süre (48 saat) PEMF maruziyetinin SK-N-SH insan nöroblastoma hücresinde apoptoz mekanizmasına olası etkileri farklı tekniklerle araştırılmıştır. Hücreler kontrol grubu, PEMF maruziyetinin olmadığı SK-N-SH hücre grubu, ve PEMF’ye 48 saat maruz bırakılan SK-N-SH hücre grubu olmak üzere üçe ayrılmıştır. Hücre canlılığı, apoptoz tayini, kaspaz-8 mRNA düzeyi ve kaspaz-8 protein ekspresyonu sırasıyla alamar mavisi, akış sitometri, qRT-PCR ve Western-Blot teknikleriyle belirlenmiştir. Uzun süreli PEMF maruziyetinin insan nöroblastoma hücresinde hücre canlılığını belirgin şekilde azaltıp hücreleri daha fazla erken apoptoza uğratarak hücreleri apoptoza sürüklediği ve bu mekanizmanın kaspaz-8 mRNA düzeyinde ve protein ekspresyon seviyesinde artışla ilişkili olabileceği gösterilmiştir

Genetic relationship between Kangal, Akbash and other dog populations

Kangal and Akbash dogs are the two well-known shepherd dog breeds in Turkey. In order to contribute to the understanding of the genetic relationship between Kangal dogs, Akbash dogs and the dogs from different regions of Eurasia, 585 base pair (bp) segment of mitochondrial DNA (mtDNA) control region was sequenced from Kangals and Akbashes. Sequences of the Kangal and Akbash dogs examined in the present study were comparatively examined with those of previous studies on dogs. Consensus neighbour-joining tree with bootstrapping, which is constructed based on pairwise Fst values between populations, indicated that Kangal dogs and Akbash dogs are on different branches of the tree. Furthermore, the nodes of these branches were supported with high bootstrap values. In conclusion, the present study indicated that Kangal and Akbash dogs might have descended maternally from different origins along the evolutionary history of domestic dogs

Sıçanlarda mekansal bellekteki bireysel varyasyonun moleküler temelinin araştırılması.

Despite very extensive studies related to molecular processes underlying memory formation, still little known about the potential differences in the brain biochemistry between “good” and “poor” learners belonging to a random population of young animals. In the present study, an attempt was taken to correlate the individual variation in short- and long-term spatial memory in three different lines of young, healthy rats: inbred Wistar (W), outcrossed Wistar/Spraque Dawley (W/S) and pigmented Long-Evans rats, with hippocampal levels of selected enzymes known as “memory molecules” including neuronal (n), endothelial (e) and inducible (i) NOS, CaMKIIα, PKA and ChAT. Additionally, in order to indirectly estimate the activity of CaMKIIα and PKA, hippocampal levels of their phosphorylated forms (pCaMKIIα and pPKA) were assessed. Rats were classified as “good” and “poor” learners on the basis of their performance in a partially baited 12-arm radial maze. The hippocampal protein levels were measured using Western Blot technique. In addition to individual variation in animals’ learning capacity, strain-depended differences have also been observed. Deficient performance recorded in inbred W rats compared to outcrossed W/S rats, and “poor” learners from both rat groups had predominantly related to the higher frequency of reference memory errors. The results of biochemical assays showed strain-depended differences in the NOS expression. The overall NOS levels were significantly higher in outcrossed W/S rats compared to inbred W rats. In both rat lines, the rate of learning positively correlated with hippocampal levels of nNOS and negatively correlated with iNOS levels. Hippocampal eNOS levels correlated negatively with animals’ performance but only in the W rats. These results suggested that all 3 NOS isoforms are implemented in the learning process playing, however, different roles in neural signaling. Experiments carried out on Long-Evans rats did not reveal a significant difference in the basal hippocampal levels of the CaMKIIα, however, the level of the pCaMKIIα, was significantly higher in “good” learners. Also, hippocampal levels of both PKA and pPKA, as well as that of ChAT were significantly higher in “good” as compared to “poor” learners. Taken together, the latter findings indicate that low hippocampal expression of PKA and ChAT as well as low CaMKIIα or PKA activation may cause learning deficits in random population of young rats, and thus, these enzymes can be considered target molecules when looking for cognitive enhancers to treat memory deficits in young subjects.Ph.D. - Doctoral Progra

α-Actinin Anchors PSD-95 at Postsynaptic Sites

Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites