T1 - Synthesis and Turnover of Membrane Proteins in Rat Liver
T1 - The integrity of liver protein synthesis in male rats treated with 1,2-dibromo-3-chloropropane
MEASUREMENT OF SYNTHESIS RATES OF LIVER-PRODUCED PLASMA PROTEINS.
Cancer is defined by the American Cancer Society asa group of diseases characterized by the uncontrolled growth andspread of abnormal cells. The World Health Organization (WHO)states that one defining feature of cancer is the rapid creation ofabnormal cells that grow beyond their usual boundaries, and whichcan then invade adjoining parts of the body and spread to otherorgans. This growth is caused by either external factors (tobacco,infectious organisms and an unhealthy diet), or by internal factors(inherited genetic mutations, hormones, and immune conditions)().
The replacement of the choline moiety of miltefosinewith a piperidine scaffold resulted in D-21266 (perifosine), acompound with a better metabolic stability, and a significantlyimproved gastrointestinal tract tolerance. Perifosine has displayedsignificant anti-proliferative activity and triggers apoptosis and in several human tumor modelsystems. Perifosine has been tested in several clinical trialsagainst a large variety of tumors. As a single therapy, perifosineproved useful only in sarcoma and Waldenstrom macroglobulinemia. Itis currently in clinical development for the treatment ofcolorectal cancer in combination with capecitabine and of multiplemyeloma in combination with bortezomib and dexamethasone or incombination with lenalidomide and dexamethasone (). Perifosine has been tested incombination with sorafenib, sunitinib, paclitaxel, docetaxel,lenalinomide or gemcitabine in various other types of cancer().
Measurement of protein turnover in rat liver.
AB - The kinetics of synthesis and degradation of the protein constituents of nuclear membranes, endoplasmic reticulum membranes (rough-surfaced microsomes), Golgi apparatus membranes and plasma membranes were determined following a single administration of L-[guanido-14C] arginine by intraperitoneal injection. Membrane protein was determined as the fraction which resists sonication and sequential extrations with 1.5 MKC1, 0.1% deoxycholate and water to remove intravesicular, intracisternal (secretory), nucleo-, adsorbed and ribosome-associated proteins. The order of maximum labeling of membrane proteins was a) endoplasmic reticulum (nuclear membrane), b) Golgi apparatus, and c) plasma membrane. Rapid decreases in specific radioactivity followed maximal labeling of endoplasmic reticulum and Golgi apparatus membranes. These rapid turnover components of endoplasmic reticulum and Golgi apparatus were sufficient to account for labeling of plasma membranes via a flow mechanism. Incorporation of radioactivity into plasma membranes showed two distinct phases. The ultrastructural features underlying the biphasic pattern of incorporation into plasma membranes are discussed. Following initial incorporation and rapid turnover, membrane proteins were characterized by degradation kinetics approximating 1st order. Rates of degradation for Golgi apparatus and plasma membranes were faster than those for nuclear envelope and endoplasmic reticulum membranes. Assuming steady state conditions, an absolute synthetic rate of 7.1 mpg/min/avergage hepatocyte was calculated for membrane proteins of the plasma membrane. The results are compatible with intracellular movement and conversion of rough endoplasmic reticulum to plasma membrane via the membranes of the Golgi apparatus, i. e., membrane flow. Additionally, the kinetics indicate that membrane synthesis and transfer is restricted to specific parts of the endoplasmic reticulum and Golgi apparatus.
Synthesis and/or collection of amino acids is critical for cell survival. They not only serve as the building blocks for proteins but also as starting points for the synthesis of many important cellular molecules including vitamins and nucleotides.
Regulation of synthesis and turnover of ferritin in rat liver.
Arencibia JM, Pastor-Flores D, Bauer AF,Schulze JO and Biondi RM: AGC protein kinases: From structuralmechanism of regulation to allosteric drug development for thetreatment of human diseases. Biochim Biophys Acta. 1834.1302–1321.2013.
Screening of the National Cancer Institute (NCI)Diversity Set led to the identification of API-2 [(Triciribine(TCN), NSC 154020] that potently inhibited Akt signaling in humancancer cells, leading to the inhibition of cell growth and theinduction of apoptosis ().TCN is a tricyclic purine nucleoside derivative () that is metabolically activatedinside cells by adenosine kinase to its monophosphate activeanalog, TCN-P (). Surfaceplasmon resonance and nuclear magnetic resonance spectroscopy havedemonstrated that TCN-P, but not TCN, binds to the PH domain of Aktin the vicinity of the PIP3 binding pocket, thereby preventing Aktphosphorylation and subsequent activation. The proposed mechanismof TCN-P Akt inhibition is by preventing PIP3 from recruiting Aktto the plasma membrane, either by competing with PIP3 for bindingto PH domain or by binding to region that induces conformationalchanges that hinder PIP3 activation (). Treatment of T cell acutelymphocytic leukemia cells with 10 μM TCN has been shown to inhibitAkt phosphorylation and its downstream signaling, causing cellcycle arrest and caspase-dependent apoptosis (). In prostate cancer cells, TCN wasshown to increase the apoptosis induced by the death receptorpathway (). TCN and TCN-Pwere subjected to several clinical trials against various solidneoplasms and hematological malignancies, but their efficacy islimited due to their toxicity (). The combination treatment of TCNwith other anticancer agents proved to be a better solution thantreatment with TCN alone ().
Protein turnover and the regulation of enzyme levels in rat liver.
Genetic regulatory mechanisms in the synthesis of proteins.
T1 - Effects of cytochalasin B on the synthesis and secretion of plasma proteins by developing rat liver
Steroid induction of porphyrin synthesis in liver cell culture.
THE ROLES OF SYNTHESIS AND DEGRADATION IN THE CONTROL OF RAT LIVER TRYPTOPHAN PYRROLASE.
Effect of drugs on heme synthesis in the liver.
Studies of the stability in vivo and in vitro of rat liver tryptophan pyrrolase.
Effect of tryptophan on polyribosomes and protein synthesis in liver.
mTOR is a downstream member of the PI3K/Akt andadenosine monophosphate-activated protein kinase pathways, and is akey regulator of cell growth and metabolism. mTOR () is a component of two similarcomplexes: mTORC1, which promotes mRNA translation and proteinsynthesis by the phosphorylation of ribosomal protein S6 kinase(S6K1) and eIF4E binding protein 1 (4E-BP1) and mTORC2, whichorganizes the cellular actin cytoskeleton and regulates Aktphosphorylation ().
Albumin synthesis in perfused liver of normal and nephrotic rats.
Induction of enhanced net synthesis of fibrinogen, alpha1-acid glycoprotein, alpha2 (acute phase)-globulin, and haptoglobin by amino acids and hormones during perfusion of the isolated normal rat liver.
Regulation of ferritin synthesis in rat liver.
Studies have proven that the Akt signaling cascadeis frequently impaired in many types of cancer and, in some cases,that it is associated with tumor aggressiveness. These are thereasons for considering this signaling pathway as a strong targetcandidate for cancer therapy or even cancer prevention (,).
Metabolic Functions of the Liver - Colorado State University
The serine/threonine kinase Akt, also known asprotein kinase B or PKB, with three isoforms (Akt1, Akt2 and Akt3),plays a critical role in regulating diverse cellular functions() including cellsize/growth, proliferation, survival, glucose metabolism, genomestability, transcription and protein synthesis, andneovascularization (). One of themajor functions of Akt/PKB is to promote growth factor-mediatedcell survival, to promote cell proliferation and to inhibitapoptosis through the inactivation of pro-apoptotic proteins, suchas Bad (Bcl-2 antagonist of cell death) and mouse double minute 2homolog (MDM2; which causes the degradation of p53) ().
15/01/2018 · Metabolic Functions of the Liver
Over the past decades, a growing body of evidencehas indicated that cancer patients can be cured by novel moleculartarget therapies due to the molecular characterization of the tumorfrom each patient. The phosphatidylinositol 3-kinase (PI3K)/Aktpathway is aberrantly activated in several types of cancers andtargeting this pathway with drug inhibitors may result in moreeffective anticancer treatment for both solid and hematologictumors (). In this review, recentdata regarding the regulation of the PI3K/Akt signal transductionpathway and its involvement in the development and progressioncancer are discussed. Furthermore, the most relevant studiesfocusing on the specific action of new molecular targeted agentsare discussed.
"I have always been impressed by the quick turnaround and your thoroughness. Easily the most professional essay writing service on the web."
"Your assistance and the first class service is much appreciated. My essay reads so well and without your help I'm sure I would have been marked down again on grammar and syntax."
"Thanks again for your excellent work with my assignments. No doubts you're true experts at what you do and very approachable."
"Very professional, cheap and friendly service. Thanks for writing two important essays for me, I wouldn't have written it myself because of the tight deadline."
"Thanks for your cautious eye, attention to detail and overall superb service. Thanks to you, now I am confident that I can submit my term paper on time."
"Thank you for the GREAT work you have done. Just wanted to tell that I'm very happy with my essay and will get back with more assignments soon."