Cell cycle and cancer

Hücre çogalması ve hücre siklusunun ilerlemesi büyümenin kontrolünde rolü olan genlerin ekspresyonu ile baglantılıdır. Ökaryot hücre siklusuM(mitoz) G , S ve G fazlarından olusmaktadır. Bu süreçte hücre uyarımı ve büyüme meydana gelir veya hücre G fazında durmaktadır. Hücre siklusunda G -S geçisinde, G -Mgeçisinde ve metafaz-anafaz geçisinde kontrol noktaları bulunmaktadır. Hücre siklusu siklin bagımlı kinazlar (cdk, katalitik altbirim) ve siklin (cyc, düzenleyici altbirim) tarafından kontrol edilmektedir. Hücre homeostazisi hücre çogalması, büyümenin durdurulması ve apoptozis (programlı hücre ölümü) ile sürdürülmektedir. Hücre siklusu içindeki olayları düzenleyen ve kontrol eden etkilesimler çok sayıda ve komplekstir. Hücre siklusunun düzenlenmesindeki hatalar hücre bölünmesinin kontrolunun bozulmasına neden olur. Hücre siklusu kontrol noktalarında degisimler kanser gelisimine neden olabilir. Kanser gelisiminde tümör baskılayıcı fonksiyon, DNA onarımı ve apoptozis kritik yolaklardır.Proliferation and cell cycle progression are linked to the expression of genes associated with growth control. The eucaryotic cell cycle consists of an M (mitotic) phase, a G phase, the S phase and G phase. Non-dividing cells exist at G . Cell cycle is regulated by several critical cell cycle check points These are G -S check point, G -M check point and metaphase-anaphase check point. Cell cycle is controlled by the cycline dependent kinases (cdk, catalytic subunit) and cyclins (cyc, regulatory subunit). Homeostasis is within a cell is regulated by the balance between proliferation, growth arrest and apopto sis. Defects in cell cycle regulation inhibit controls for cell division. Alterations of cell cycle check points might result in cancer. The interactions which control and regulate the cascade of events within cell cycle are numerous and complex. Tumor supression of growth arrest, DNA repair and apoptosis, are all critical pathways in the development of cancers

Distribution of Muscarinic Acethylcholine Receptors and Related Signal

Muscarinic receptors are members of G protein coupled receptor family. Molecularcloning studies indicate five intronless genes that encode five muscarinic receptorglycoproteins. Muscarinic receptor genes are fairly similar between species.Muscarinic receptors mediate many cellular responses by activating second messengersystems through the action of G proteins. Muscarinic receptors are divided into twofunctional categories; M1, M3, and M5 receptors preferentially couple to the Gq/11protein which activates phospholipase C, whereas M2 and M4 receptors preferentiallycouple to Gi/o protein, which inhibits adenylate cyclase activity. Muscarinic receptorsare distributed widely in central and peripheral tissues. M1 receptors are found in theforebrain, especially in the hippocampus and cerebral cortex. M2 receptors are foundheart and brainstem, M3 receptors are found in the smooth muscle, exocrine glandsand cerebral cortex. M4 receptors are seen in the neo-striatum and M5 receptor mRNAis found in the substantia nigra. M2 receptors in the CNS are the main muscarinicacethylcholine receptors that mediate acethylcholine induced MAP kinase activationwhich is necessary for memory. The brain M2 receptors play important role forantinociception. In addition, M2 receptors are essential for muscarinic acethylcholinereceptor-dependent bradycardia and agonist induced contraction of stomach, urinarybladder and trachea. M3 receptors are involved in salivary secretion, pupillaryconstriction and bladder detrusor contraction. Brain M4 receptors are participate inthe modulation of central dopaminergic responses and regulate peripheral smoothmuscle tone. M5 receptors may regulate dopamine release. But this regulation isnot fully understood. Muscarinic receptors are involved in different pathologicalconditions such as heart failure, Alzheimer disease and asthma. Identification ofmuscarinic receptor subtypes expressed in various cells and tissues is important inthe de-velopment of selective drugs

Methoctramine and gallamine inhibit PI hydrolysis in guinea-pig gallbladder

The present study aimed to determine the effect Of two M-2/M-4-selective muscarinic receptor antagonists on blocking the hydrolysis of carbachol (CCh) stimulated phospho-inositide (PI) breakdown in order to address the possibility that a muscarinic receptor other than the M-3 receptor is involved in PI hydrolysis in this tissue. Gallbladder tissue slices labeled with myo-[2-H-3] inositol were incubated with increasing concentrations of antagonists and agonist. After the reactions were terminated by the addition of chloroform/methanol, labeled inositol phosphates were separated using anion exchange chromatography. Muscarinic M-2 antagonists methoctramine and gallamine both inhibited carbachol-induced PI breakdown at high concentrations, with 109 IC50 values of -5.145 and -6.049, respectively. Gallamine at 10(-5) M concentration failed to displace the dose-response curve for carbachol-induced accumulation of inositol triphosphate (IP3). Our data suggest that M-3 receptors play a major role in stimulation of PI hydrolysis in the guinea-pig gallbladder. (c) 2005 Elsevier Inc. All rights reserved

Post-Traumatic Stress Disorder: The Importance of Apoptosis

Apoptosis is programmed cell death, which actively occurs in many physiological processes. It can be triggered in two ways: (i) defects in growth factor, DNA damage, and other many factors that can cause cellular stress, which is an intracellular pathway, and (ii) ligand binding to death receptors and activation of caspases. The apoptotic cell count can be determined by the health of the whole organism. A higher apoptotic ratio can indicate a decrease in the number of cells and tissue damage, while a lower apoptotic ratio can indicate an increase in the number of cells. Irregularity in apoptotic signals can play primary or secondary roles in various diseases/disorders. Research on apoptosis depends on neurodegeneration has been initiated in the past few years. Definition of apoptotic signal pathways and apoptotic regulation and determination of pro- and anti-apoptotic genes are the main topics that have accelerated research on apoptosis. Neurodegenerative disorders such as post-traumatic stress disorder neuronal damage associated with changes in brain structure and function may be related to the mitochondrial stresses. In physiological conditions, apoptosis is crucial for the organism, while in pathological conditions, apoptosis can cause uncontrolled cell division. Development of therapeutic medicine that inhibits the cell death may be the new choice of treatment for neurodegenerative diseases/disorders

M-2, M-3, and M-4 muscarinic receptors are expressed in the guinea pig gallbladder

Aim: The identity of muscarinic acetylcholine receptors (mAchR) involved in cholinergic-mediated contraction of the guinea pig gallbladder has been a matter of debate. Different groups have suggested the involvement of M-1, M-2, M-3, or M-4 receptor subtypes in the contraction of this tissue. The objective of this study was to identify the mAchR subtypes expressed in the guinea pig gallbladder by RT-PCR. Methods: Total RNA prepared from frozen guinea pig gallbladder tissue was amplified by using specific primers for the M-1-M-4 receptor subtypes. Results: M-2, M-3, and M-4 transcripts were detected in the following rank order: M-4 > M-2 > M-3. We were unable to demonstrate the expression of the M, receptor subtype in this tissue. Conclusions: Our results are in agreement with our previous binding and functional data