Explore chapters and articles related to this topic
Relaxation Oscillators
Published in James E. Ferrell, Systems Biology of Cell Signaling, 2021
The current view of regulatory circuit that drives the cell cycle is shown schematically in Figure 15.4. Oscillations are now know to be driven by the synthesis of several related mitotic cyclin proteins (cyclins B1α, B1β, B2, B4, B5, and A1, here collectively referred to as cyclin B). The cyclin B binds with high affinity to Cdk1, which is present in modest excess, and when the cyclin B–Cdk1 complex is in the right phosphorylation state, it is active as a protein kinase, phosphorylating hundreds of substrate proteins at many hundreds of phosphorylation sites. The collective effect of these phosphorylations is the dramatic cellular changes of mitotic entry, including chromatin condensation, nuclear envelope breakdown, vesiculation of the golgi, endoplasmic reticulum, and mitochondria, and reorganization of the microtubules into a football-shaped spindle.
Phytoconstituents from Neem with Multiple Activities
Published in Bhupinder Singh, Om Prakash Katare, Eliana B. Souto, NanoAgroceuticals & NanoPhytoChemicals, 2018
Suman Chaudhary, Rupinder Kaur Kanwar, Teenu Sharma, Bhupinder Singh, Jagat Rakesh Kanwar
The bioactivity of neem seed oil is mainly attributed to its rich content of azadirachtin. Azadirachtin, along with nimbolide, exerts significant cytotoxic effects on the viability of the human cervical cancer cell line (HeLa). It induces p53-dependent p21 accumulation, along with cell-cycle arrest at the G0/G1 phase, and causes decrease in cell-cycle regulatory proteins including cyclin b, PCNA, and cyclin D1. Further, it causes modifications in the nuclear morphology and induces apoptotic signals via a mitochondrial pathway (Priyadarsini et al., 2010). However, both azadirachtin and nimbolide are capable of causing toxicity since a high dose of azadirachtin (LD50 > 5000 mg/kg bw) and intraperitoneal or intravenous administration of nimbolide can cause acute toxicity in experimental animals (Glinsukon et al., 1986; Raizada et al., 2001). Another study, conducted on the bioinsecticide azadirachtin A, indicated that it is not genotoxic and has an antiproliferative effect on the Chinese hamster ovary cells (CHO) and on human lymphocytes. It modulates the first and second (M1 and M2) division metaphases, thus interfering with the cell-cycle progression (Mosesso et al., 2012). Nonetheless, extensive investigations are required on the precise molecular mechanisms, pharmacokinetics, and toxicity of these neem limonoids to explore the therapeutic and preventive potential of neem in humans.
Treatment Options for Chemical Sensitivity
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
Cyclins were identified originally as proteins in the murine invertebrate cells. The concentration of these cyclins accumulate and are destroyed periodically at defined points during the cell cycle.475 At present, eight cyclins have been identified; these are designated A, B, C, D, E, F, G1, and H based on their amino acid sequences,476,477 and in some instances, on genetic complementation experiments in yeast.474,478–480 The influences of the cyclins are expressed differently; for example, cyclin A exhibits its influence through the S-M phase481–486 of most cells, while cyclin B (which is conserved from yeasts to humans) propels cells into mitosis459,475,487. Both the A and B cyclins are degraded at the M phase by ubiquitin (Ub)-dependent proteolysis.487 G1 cyclins (CIN 1, CIN 2, CIN 3) are assumed to associate with a p34 CDC2 homologue, p34 CDC 28, driving yeast cells into S phase.488–492,499 In the Environmental Health Center-Dallas (EHC-D), clinical cases are investigated varying from surgical to environmental illnesses. However, cases involving chemical sensitivity entail the principal aspect of our practice. Over a period of 22 years, our laboratory observations show that characteristically, a percentage of the chemically sensitive individuals portray a secondary deficit which is related to immune dysfunction, principally, depression of the suppressor T-cell.493,494 Initial profiles of lymphocyte cell cycle progression, T and B lymphocytes, CMI, and hematograms of patients were compared with those taken subsequent to treatment with ALF.
Carnosic acid exhibits antiproliferative and proapoptotic effects in tumoral NCI-H460 and nontumoral IMR-90 lung cells
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Amanda Cristina Corveloni, Simone Cristine Semprebon, Adrivanio Baranoski, Bruna Isabela Biazi, Thalita Alves Zanetti, Mário Sérgio Mantovani
Cyclin-dependent kinases (CDKs) drive cell cycle progression, and changes in CDK activities are regulated by cyclins D, E, A, and B, ensuring that kinase activity is regulated in a time-specific manner (Malumbres and Barbacid 2009). In the present study, IMR-90 cells exposed to CA exhibited a decrease in mRNA levels of CCNA2, a gene that encodes cyclin A2, as well as CCNB1 and CCNB2 that encode cyclin B. Cyclins A2, B1, and B2 are essential for cell cycle progression. Cyclin A/CDK2 is important in the control of DNA replication (Yam, Fung, and Poon 2002), and together with cyclin E/CDK2, acts by limiting replication to only once per cycle (Woo and Poon 2003). Cyclin A2 also activates CDK1 at the end of the G2 phase to initiate mitosis (Malumbres and Barbacid 2009). Progression from G2 phase to M phase is driven by the activation of cyclin B/CDK1. This complex is able to promote several cellular reorganizations that occur at the beginning of mitosis, such as mitotic spindle assembly, condensation of chromosomes, nuclear envelope rupture, and cytoskeletal reorganization (Gavet and Pines 2010). Downregulation of CCNA2, CCNB1, and CCNB2 by CA may be related to cell cycle arrest at the G0/G1 and G2/M phases in IMR-90 cells. In NCI-H460 cells, no marked alterations were observed in cyclin expression, as it may be more resistant to CA treatment. Previous investigators reported that CA cell cycle arrest may be attributed to the downregulation of cyclins A2 and B, and via modulation of other cell cycle components (Cortese et al. 2016; Visanji, Thompson, and Padfield 2006). Cortese et al. (2016) demonstrated that CA initiated G2 phase arrest mediated by downregulation of cyclin B1, diminished CDK activity, and enhanced p21 levels in human glioblastoma cells. CA treatment of Caco-2 cells led to a gradual accumulation of cells prior to prometaphase that was associated with a decrease in cyclin A levels (Visanji, Thompson, and Padfield 2006).