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Neuroendocrine Factors
Published in Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan, Strength and Conditioning in Sports, 2023
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan
Cortisol (C) is a steroid hormone secreted by the zona reticularis and zona fasciculata of the adrenal cortex. Production and secretion are stimulated by adrenocorticotropic hormone (ACTH), which is released by the anterior pituitary and regulated by hypothalamic-pituitary feedback mechanisms (100, 108). Cortisol is the primary stress hormone and is involved in a number of physiological actions including fuel substrate mobilization, gluconeogenesis, and immune system suppression. Cortisol generally has anti-anabolic and catabolic effects (108, 147). These effects are mediated by gene derepression and RNA synthesis (176). The primary functions of cortisol are described in the following paragraphs.
The Future of Narcotic Addiction
Published in Albert A. Kurland, S. Joseph Mulé, Psychiatric Aspects of Opiate Dependence, 2019
Albert A. Kurland, S. Joseph Mulé
Discussing their experiments, Stevenson et al.28 point out that enthusiasts for drug interviews have often drawn attention to the fact that patients under the influence of a drug talk more freely and express emotions more abundantly than they usually do in interviews without drugs. Moreover, the improvements in feelings and symptoms after interviews with drugs are then usually attributed to the beneficial effects of emotional expression and derepression. Their studies also emphasized the importance of the interviewer’s role and whether the patient felt free or inhibited under the conditions of the interview. Furthermore, the freedom of expression was directly related to the sense of ease which the patient felt within the interview situation. The more the subject viewed the interviewer as a stranger, the more inhibited the patient’s freedom of expression would be.
Chemical Carcinogenesis as a Consequence of Alterations in the Structure and Function of DNA
Published in Philip L. Grover, Chemical Carcinogens and DNA, 2019
In addition, we do not believe, on the basis of the theory to be presented, that all carcinogenic events need both the initiation and promotion phases. There might be some which require only initiation; some which require both initiation and promotion; while others would require only promotion.** A summary of the two-stage concept of carcinogenesis is presented with the following definitions. Carcinogenesis = initiation and/or promotion.Initiation = DNA damage + “mutation fixation”.Anti-initiation = prevention of DNA damage and its repair by “error-prone” mechanisms.Promotion = gene modulation (gene repression or derepression).Antipromotion = negation of tumor promoter functions.
Endogenous retroviral proteins provide an immunodominant but not requisite antigen in a murine immunotherapy tumor model
Published in OncoImmunology, 2020
Xuan Ye, Janelle C. Waite, Ankur Dhanik, Namita Gupta, Maggie Zhong, Christina Adler, Evangelia Malahias, Min Ni, Yi Wei, Cagan Gurer, Wen Zhang, Lynn E. Macdonald, Andrew J. Murphy, Matthew A. Sleeman, Dimitris Skokos
We identified an endogenous retroviral antigen p15E as the immunodominant epitope of MC38. The endogenous viral genome is highly expressed in several tumor cell lines due to epigenetic derepression. Surprisingly, B16F1 and B16F10.9, the derivatives of a murine melanoma cell line highly expressing the endogenous viral genome, were incapable of stimulating p15E-specific JRT reporter cells. Treating them with IFNγ in vitro enhanced MHCI expression but still failed to stimulate p15E-specific reporter cells. Previously published data also suggested that p15E was expressed in B16 parental cell lines and p15E-pulsed DC vaccine or adoptive transfer of p15E-specific T cells inhibited established B16 lung metastasis.45,46 We have shown here that the p15E coding sequence is identical between MC38 and B16 cells. Interestingly, we found differences in the expression of some proteasome genes involved in endogenous processing pathway. It is possible that altered antigen processing machinery results in decreased ability of B16 cell lines to stimulate p15E-specific TCRs, which remains to be confirmed.
Drugs that target aging: how do we discover them?
Published in Expert Opinion on Drug Discovery, 2019
Cellular senescence (hereinafter, ‘senescence’) refers to a permanent state of arrested cell proliferation wherein a cell remains alive but fails to divide and reproduce. Senescent cells can be distinguished, both morphologically and through biomarkers, from either cells undergoing transient growth arrest (‘quiescence’) or terminally differentiated cells, which lose their ability to replicate once they have taken on a specialized function (e.g. red blood cells, neurons, etc.) [26]. Senescence was discovered by Leonard Hayflick and Paul Moorhead during experiments in the 1960s that uncovered the Hayflick Limit, i.e. the inability for cells to divide and reproduce more than a certain number of times in culture [27,28]. It was later determined that this type of senescence (termed ‘replicative senescence’) is a result of a DNA damage response triggered by telomere attrition during repeated replication that cannot be repaired by endogenous DNA repair machinery. Cellular senescence can also be induced in other ways, for example through mutations that produce activated oncogenes, elevated levels of reactive oxygen species (ROS), other (non-ROS producing) mitochondrial dysfunction, and DNA damage induced by ionizing radiation, genotoxic chemotherapies, or stalled replication or transcription forks; as well as through pathways that trigger derepression of the gene locus CDKN2A, leading to increased expression of the p16INK4a protein (hereinafter, ‘p16ʹ) [29].
Post-translational regulation of a Porphyromonas gingivalis regulator
Published in Journal of Oral Microbiology, 2018
Yuqing Li, Karthik Krishnan, Margaret J. Duncan
In B. fragilis and other Bacteroidetes, including the oral species Prevotella intermedia and Tannerella forsythia, rprY is adjacent to rprX, the HK partner. However, an rprX homologue is not present in P. gingivalis, and there are no proteins with any similarity in this species. Although it is possible that phosphorylation of RprY may be carried out by one of the other HKs present in the P. gingivalis genome, we were intrigued by the presence of a protein acetyltransferase (pat) gene immediately downstream from rprY, and the possibility that protein acetylation may play a role in the regulation of RprY activity. In the present study, we show that rprY and pat are co-transcribed, and that RprY is acetylated in vivo. We also show that RprY is autoacetylated in vitro by a reaction in which acetyl CoA is the acetyl donor, and that autoacetylation is enhanced by Pat and reversed by the CobB deacetylase. Furthermore, it appears that phosphorylated, that is, activated RprY is the preferred substrate for acetylation suggesting cross-talk between the protein modification activities. Finally, we show that acetylated RprY had diminished ability to bind to promoter DNA; thus, modification of regulator proteins by acetylation appears to be another mechanism to modulate their function [6], including derepression.