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Self-cytoprotection against stress: feedback regulation of heme- dependent metabolism

Schwartsburd, P.M.
Fonte: Cell Stress Society International Publicador: Cell Stress Society International
Tipo: Artigo de Revista Científica
Publicado em /01/2001 EN
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26.59%
This minireview provides insight into feedback regulation of heme-dependent metabolism as a defensive cellular response against stress. Interactions among heme-, iron-, porphyrin-, and CO/NO-dependent metabolic pathways during the stress-induced response are emphasized in the context of feedback regulation. The hypothetical model of the latter interactions is presented as tightly controlled feedback cycles.

Minireview: Obesity and LipOdystrophy—Where Do the Circles Intersect?

Chehab, Farid F.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
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26.59%
Adipose tissue is unique in that it can undergo significant hypertrophy and atrophy, resulting in wide ranges of obesities and lipodystrophies. At the base of this elasticity is the lipid-filled adipocyte, which can either overfill by storing large amounts of triglycerides or shrink to a tiny cell by depleting its lipids and as such is remarkable in sustaining insults. As a major energy reservoir, the adipocyte may hold considerable calories necessary for survival and reproduction, two functions that are essential for the survival of the species. This review will summarize some of the recent studies that have advanced our understanding of the central and peripheral mechanisms that are initiated by adipocyte-secreted factors such as leptin, adiponectin, resistin, and retinol-binding protein 4. The intersection of obesity and lipodystrophy results in insulin resistance, which may be unlocked by elucidating the roles of these factors in pathways that control insulin sensitivity and glucose uptake.

Minireview: Mitochondrial Energetics and Insulin Resistance

Civitarese, Anthony E.; Ravussin, Eric
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
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26.59%
Obesity, insulin resistance, type 2 diabetes mellitus, and aging are associated with impaired skeletal muscle oxidation capacity, reduced mitochondrial content, and lower rates of oxidative phosphorylation. Several studies have reported ultrastructural abnormalities in mitochondrial morphology and reductions in mitochondrial mass in insulin-resistant individuals. From lower organisms to rodents, mitochondrial membrane structure, function, and programmed cell death are regulated in part by the balance between the opposing forces of mitochondrial fusion and fission, suggesting they may also play an important role in human physiology.

Minireview: Nuclear Receptors and Breast Cancer

Conzen, Suzanne D.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
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26.59%
Until recently, the study of nuclear receptor (NR) function in breast cancer biology has been largely limited to estrogen and progesterone receptors. The development of reliable gene expression arrays, real-time quantitative RT-PCR, and immunohistochemical techniques for studying NR superfamily members in primary human breast cancers has now revealed the presence and potential importance of several additional NRs in the biology of breast cancer. These include receptors for steroid hormones (including androgens and corticosteroids), fat-soluble vitamins A and D, fatty acids, and xenobiotic lipids derived from diet. It is now clear that after NR activation, both genomic and nongenomic NR pathways can coordinately activate growth factor signaling pathways. Advances in our understanding of both NR functional networks and epithelial cell growth factor signaling pathways have revealed a frequent interplay between NR and epithelial cell growth factor family signaling that is clinically relevant to breast cancer. Understanding how growth factor receptors and their downstream kinases are activated by NRs (and vice-versa) is a central goal for maximizing treatment opportunities in breast cancer. In addition to the estrogen receptor, it is predicted that modulating the activity of other NRs will soon provide novel prevention and treatment approaches for breast cancer patients.

Minireview: The Intersection of Steroid Receptors with Molecular Chaperones: Observations and Questions

Smith, David F.; Toft, David O.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
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26.59%
An involvement of molecular chaperones in the action and well-being of steroid receptors was recognized early in the molecular era of hormone research. However, this has continued to be a topic of much enquiry and some confusion. All steroid receptors associate with heat shock protein 90, the main character of a series of multiprotein chaperone complexes generally referred to as the “heat shock protein 90 chaperoning machine.” Receptor association with chaperones occurs in an ordered, step-wise fashion and is necessary for the maintenance of unliganded receptor in a state ready to bind and respond to hormone. Chaperones additionally modulate how receptors respond to hormone and activate target genes. Although much is known about the participants in this chaperoning process and the consequences of chaperoning, many key questions remain unanswered, particularly those concerning molecular mechanisms, cellular dynamics, and the functions of an array of cochaperone proteins. Here, we point out several areas in need of investigation to encourage new ideas and participants in this burgeoning field.

Minireview: How Peptide Hormone Vesicles Are Transported to the Secretion Site for Exocytosis

Park, Joshua J.; Loh, Y. Peng
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
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26.59%
Post-Golgi transport of peptide hormone-containing vesicles from the site of genesis at the trans-Golgi network to the release site at the plasma membrane is essential for activity-dependent hormone secretion to mediate various endocrinological functions. It is known that these vesicles are transported on microtubules to the proximity of the release site, and they are then loaded onto an actin/myosin system for distal transport through the actin cortex to just below the plasma membrane. The vesicles are then tethered to the plasma membrane, and a subpopulation of them are docked and primed to become the readily releasable pool. Cytoplasmic tails of vesicular transmembrane proteins, as well as many cytosolic proteins including adaptor proteins, motor proteins, and guanosine triphosphatases, are involved in vesicle budding, the anchoring of the vesicles, and the facilitation of movement along the transport systems. In addition, a set of cytosolic proteins is also necessary for tethering/docking of the vesicles to the plasma membrane. Many of these proteins have been identified from different types of (neuro)endocrine cells. Here, we summarize the proteins known to be involved in the mechanisms of sorting various cargo proteins into regulated secretory pathway hormone-containing vesicles...

Minireview: The PGC-1 Coactivator Networks: Chromatin-Remodeling and Mitochondrial Energy Metabolism

Lin, Jiandie D.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Transcriptional coactivators and corepressors are emerging as important regulators of energy metabolism and other biological processes. These factors exert their effects on the transcription of target genes through interaction with selective transcription factors and the recruitment of chromatin-remodeling complexes. Recent genetic and biochemical analyses of the peroxisomal proliferator-activated receptor-γ coactivator 1 networks provide novel mechanistic insights regarding their role in the control of mitochondrial oxidative metabolism. These coactivators integrate tissue metabolic functions in response to nutritional signals as well as circadian timing cues. In contrast to coactivators, transcriptional corepressors have been demonstrated to play an opposite role in the control of mitochondrial biogenesis and respiration. The balance of these coactivator and corepressor proteins and, more importantly, their access to specific transcriptional partners are predicted to dictate the epigenetic states of target genes as well as the metabolic phenotype of the cells. This review highlights the biological role and mechanistic basis of the peroxisomal proliferator-activated receptor-γ coactivator 1 networks in the regulation of chromatin-remodeling and mitochondrial oxidative metabolism.

Minireview: Protein Arginine Methylation of Nonhistone Proteins in Transcriptional Regulation

Lee, Young-Ho; Stallcup, Michael R.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Endocrine regulation frequently culminates in altered transcription of specific genes. The signal transduction pathways, which transmit the endocrine signal from cell surface to the transcription machinery, often involve posttranslational modifications of proteins. Although phosphorylation has been by far the most widely studied protein modification, recent studies have indicated important roles for other types of modification, including protein arginine methylation. Ten different protein arginine methyltransferase (PRMT) family members have been identified in mammalian cells, and numerous substrates are being identified for these PRMTs. Whereas major attention has been focused on the methylation of histones and its role in chromatin remodeling and transcriptional regulation, there are many nonhistone substrates methylated by PRMTs. This review primarily focuses on recent progress on the roles of the nonhistone protein methylation in transcription. Protein methylation of coactivators, transcription factors, and signal transducers, among other proteins, plays important roles in transcriptional regulation. Protein methylation may affect protein-protein interaction, protein-DNA or protein-RNA interaction, protein stability, subcellular localization...

Minireview: Meeting the Demand for Insulin: Molecular Mechanisms of Adaptive Postnatal ß-Cell Mass Expansion

Sachdeva, Mira M.; Stoffers, Doris A.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Type 2 diabetes results from pancreatic ß-cell failure in the setting of insulin resistance. This model of disease progression has received recent support from the results of genome-wide association studies that identify genes potentially regulating ß-cell growth and function as type 2 diabetes susceptibility loci. Normal ß-cell compensation for an increased insulin demand includes both enhanced insulin-secretory capacity and an expansion of morphological ß-cell mass, due largely to changes in the balance between ß-cell proliferation and apoptosis. Recent years have brought significant progress in the understanding of both extrinsic signals stimulating ß-cell growth as well as mediators intrinsic to the ß-cell that regulate the compensatory response. Here, we review the current knowledge of mechanisms underlying adaptive expansion of ß-cell mass, focusing on lessons learned from experimental models of physiologically occurring insulin-resistant states including diet-induced obesity and pregnancy, and highlighting the potential importance of interorgan cross talk. The identification of critical mediators of islet compensation may direct the development of future therapeutic strategies to enhance the response of ß-cells to insulin resistance.

Minireview: Fetal-Maternal Hormonal Signaling in Pregnancy and Labor

Mendelson, Carole R.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Mechanisms underlying the initiation of parturition remain unclear. Throughout most of pregnancy, uterine quiescence is maintained by elevated progesterone acting through progesterone receptor (PR). Although in most mammals, parturition is associated with a marked decline in maternal progesterone, in humans, circulating progesterone and uterine PR remain elevated throughout pregnancy, suggesting a critical role for functional PR inactivation in the initiation of labor. Both term and preterm labor in humans and rodents are associated with an inflammatory response. In preterm labor, intraamniotic infection likely provides the stimulus for increased amniotic fluid interleukins and migration of inflammatory cells into the uterus and cervix. However, at term, the stimulus for this inflammatory response is unknown. Increasing evidence suggests that the developing fetus may produce physical and hormonal signals that stimulate macrophage migration to the uterus, with release of cytokines and activation of inflammatory transcription factors, such as nuclear factor κB (NF-κB) and activator protein 1 (AP-1), which also is activated by myometrial stretch. We postulate that the increased inflammatory response and NF-κB activation promote uterine contractility via 1) direct activation of contractile genes (e.g. COX-2...

Thematic Minireview Series: Metals in Biology*

Guengerich, F. Peter
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
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36.96%
Metals have important roles in biochemistry ranging from essential to toxic. This prologue introduces the second of the Thematic Minireview Series on Metals in Biology, which includes minireviews on five metals: iron, zinc, nickel, vanadium, and arsenic. Three of the minireviews are focused on the roles of the metals in enzymes (iron, nickel, and vanadium). Zinc deficiency is discussed in another, and the arsenic minireview deals with the toxic and some potentially useful applications of the biological effects.

Exploring the Chemistry and Biology of Vanadium-dependent Haloperoxidases*

Winter, Jaclyn M.; Moore, Bradley S.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Nature has developed an exquisite array of methods to introduce halogen atoms into organic compounds. Most of these enzymes are oxidative and require either hydrogen peroxide or molecular oxygen as a cosubstrate to generate a reactive halogen atom for catalysis. Vanadium-dependent haloperoxidases contain a vanadate prosthetic group and utilize hydrogen peroxide to oxidize a halide ion into a reactive electrophilic intermediate. These metalloenzymes have a large distribution in nature, where they are present in macroalgae, fungi, and bacteria, but have been exclusively characterized in eukaryotes. In this minireview, we highlight the chemistry and biology of vanadium-dependent haloperoxidases from fungi and marine algae and the emergence of new bacterial members that extend the biological function of these poorly understood halogenating enzymes.

Chromosome End Maintenance by Telomerase*

Osterhage, Jennifer L.; Friedman, Katherine L.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Telomeres, protein-DNA complexes at the ends of eukaryotic linear chromosomes, are essential for genome stability. The accumulation of chromosomal abnormalities in the absence of proper telomere function is implicated in human aging and cancer. Repetitive telomeric sequences are maintained by telomerase, a ribonucleoprotein complex containing a reverse transcriptase subunit, a template RNA, and accessory components. Telomere elongation is regulated at multiple levels, including assembly of the telomerase holoenzyme, recruitment of telomerase to the chromosome terminus, and telomere accessibility. This minireview provides an overview of telomerase structure, function, and regulation and the role of telomerase in human disease.

Minireview: The Case for Obesogens

Grün, Felix; Blumberg, Bruce
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.59%
Obesity and obesity-related disorders, such as type 2 diabetes, hypertension, and cardiovascular disease, are epidemic in Western countries, particularly the United States. The conventional wisdom holds that obesity is primarily the result of a positive energy balance, i.e. too many calories in and too few calories burned. Although it is self-evident that fat cannot be accumulated without a higher caloric intake than expenditure, recent research in a number of laboratories suggests the existence of chemicals that alter regulation of energy balance to favor weight gain and obesity. These obesogens derail the homeostatic mechanisms important for weight control, such that exposed individuals are predisposed to weight gain, despite normal diet and exercise. This review considers the evidence for obesogens, how they might act, and where future research is needed to clarify their relative contribution to the obesity epidemic.

Type II Transmembrane Serine Proteases*

Bugge, Thomas H.; Antalis, Toni M.; Wu, Qingyu
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.82%
Analysis of genome and expressed sequence tag data bases at the turn of the millennium unveiled a new protease family named the type II transmembrane serine proteases (TTSPs) in a Journal of Biological Chemistry minireview (Hooper, J. D., Clements, J. A., Quigley, J. P., and Antalis, T. M. (2001) J. Biol. Chem. 276, 857–860). Since then, the number of known TTSPs has more than doubled, and more importantly, our understanding of the physiological functions of individual TTSPs and their contribution to human disease has greatly increased. Progress has also been made in identifying molecular substrates and endogenous inhibitors. This minireview summarizes the current knowledge of the rapidly advancing TTSP field.

Minireview: Physiological and Pathological Actions of RAS in the Ovary

Fan, Heng-Yu; Richards, JoAnne S.
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.82%
The small G proteins of the RAS superfamily act as molecular switches in the transduction of cellular signals critical for a wide range of normal developmental events as well as pathological processes. However, the functions of Ras genes in ovarian cells have only started to be unveiled. RAS, most likely KRAS that is highly expressed in granulosa cells of growing follicles, appears crucial for mediating the gonadotropin-induced events associated with the unique physiological process of ovulation. By contrast, conditional expression of a constitutively active KrasG12D mutant in granulosa cells results in ovulation defects due to the complete disruption of normal follicular growth, cessation of granulosa cell proliferation, and blockage of granulosa cell apoptosis and differentiation. When the tumor suppressor Pten is disrupted conditionally in the KrasG12D-expressing granulosa cells, granulosa cell tumors fail to develop. However, ovarian surface epithelial cells expressing the same Pten;KrasG12D mutations rapidly become ovarian surface epithelial serous cystadenocarcinomas. In this minireview, we summarize some of the physiological as well as pathological functions of RAS in the rodent ovary, discuss the implications of the KrasG12D mutant mouse models for understanding human diseases such as premature ovarian failure and ovarian cancers...

Minireview: The Role of the Autonomic Nervous System in Mediating the Glucagon Response to Hypoglycemia

Taborsky, Gerald J.; Mundinger, Thomas O.
Fonte: Endocrine Society Publicador: Endocrine Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.96%
In type 1 diabetes, the impairment of the glucagon response to hypoglycemia increases both its severity and duration. In nondiabetic individuals, hypoglycemia activates the autonomic nervous system, which in turn mediates the majority of the glucagon response to moderate and marked hypoglycemia. The first goal of this minireview is therefore to illustrate and document these autonomic mechanisms. Specifically we describe the hypoglycemic thresholds for activating the three autonomic inputs to the islet (parasympathetic nerves, sympathetic nerves, and adrenal medullary epinephrine) and their magnitudes of activation as glucose falls from euglycemia to near fatal levels. The implication is that their relative contributions to this glucagon response depend on the severity of hypoglycemia. The second goal of this minireview is to discuss known and suspected down-regulation or damage to these mechanisms in diabetes. We address defects in the central nervous system, the peripheral nervous system, and in the islet itself. They are categorized as either functional defects caused by glucose dysregulation or structural defects caused by the autoimmune attack of the islet. In the last section of the minireview, we outline approaches for reversing these defects. Such reversal has both scientific and clinical benefit. Scientifically...

Adverse Effects of Antimicrobials via Predictable or Idiosyncratic Inhibition of Host Mitochondrial Components

Barnhill, Alison E.; Brewer, Matt T.; Carlson, Steve A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /08/2012 EN
Relevância na Pesquisa
26.82%
This minireview explores mitochondria as a site for antibiotic-host interactions that lead to pathophysiologic responses manifested as nonantibacterial side effects. Mitochondrion-based side effects are possibly related to the notion that these organelles are archaic bacterial ancestors or commandeered remnants that have co-evolved in eukaryotic cells; thus, this minireview focuses on mitochondrial damage that may be analogous to the antibacterial effects of the drugs. Special attention is devoted to aminoglycosides, chloramphenicol, and fluoroquinolones and their respective single side effects related to mitochondrial disturbances. Linezolid/oxazolidinone multisystemic toxicity is also discussed. Aminoglycosides and oxazolidinones are inhibitors of bacterial ribosomes, and some of their side effects appear to be based on direct inhibition of mitochondrial ribosomes. Chloramphenicol and fluoroquinolones target bacterial ribosomes and gyrases/topoisomerases, respectively, both of which are present in mitochondria. However, the side effects of chloramphenicol and the fluoroquinolones appear to be based on idiosyncratic damage to host mitochondria. Nonetheless, it appears that mitochondrion-associated side effects are a potential aspect of antibiotics whose targets are shared by prokaryotes and mitochondria—an important consideration for future drug design.

Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography

Grose, Charles
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2012 EN
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26.82%
The goal of this minireview is to provide an overview of varicella-zoster virus (VZV) phylogenetics and phylogeography when placed in the broad context of geologic time. Planet Earth was formed over 4 billion years ago, and the supercontinent Pangaea coalesced around 400 million years ago (mya). Based on detailed tree-building models, the base of the phylogenetic tree of the Herpesviridae family has been estimated at 400 mya. Subsequently, Pangaea split into Laurasia and Gondwanaland; in turn, Africa rifted from Gondwanaland. Based on available data, the hypothesis of this minireview is that the ancestral alphaherpesvirus VZV coevolved in simians, apes, and hominins in Africa. When anatomically modern humans first crossed over the Red Sea 60,000 years ago, VZV was carried along in their dorsal root ganglia. Currently, there are five VZV clades, distinguishable by single nucleotide polymorphisms. These clades likely represent continued VZV coevolution, as humans with latent VZV infection left Arabia and dispersed into Asia (clades 2 and 5) and Europe (clades 1, 3, and 4). The prototype VZV sequence contains nearly 125,000 bp, divided into 70 open reading frames. Generally, isolates within a clade display >99.9% identity to one another...

Dormancy models for Mycobacterium tuberculosis: A minireview

Alnimr, Amani M.
Fonte: Sociedade Brasileira de Microbiologia Publicador: Sociedade Brasileira de Microbiologia
Tipo: Artigo de Revista Científica
Publicado em 01/07/2015 EN
Relevância na Pesquisa
26.82%
Dormancy models for Mycobacterium tuberculosis play important roles in understanding various aspects of tuberculosis pathogenesis and in the testing of novel therapeutic regimens. By simulating the latent tuberculosis infection, in which the bacteria exist in a non-replicative state, the models demonstrate reduced susceptibility to antimycobacterial agents. This minireview outlines the models available for simulating latent tuberculosis both in vitro and in several animal species. Additionally, this minireview discusses the advantages and disadvantages of these models for investigating the bacterial subpopulations and susceptibilities to sterilization by various antituberculosis drugs.