scholarly journals Prohibitin: A hypothetical target for sex-based new therapeutics for metabolic and immune diseases

2019 ◽  
Vol 244 (2) ◽  
pp. 157-170 ◽  
Author(s):  
Suresh Mishra ◽  
BL Grégoire Nyomba
Keyword(s):  
Sex Differences ◽  
Sex Steroids ◽  
Immune Cell ◽  
Cell Types ◽  
Immune Functions ◽  
Evolutionarily Conserved ◽  
Health And Disease ◽  
Multiple Cell ◽  
Membrane Signaling

Adipose and immune functions display sex differences and are influenced by sex steroid hormones in health and disease. However, effector molecules that mediate the effects of sex steroids and determine sex differences in adipocytes and immune cells are largely unknown. Sex differences are known to exist in mitochondrial biology, and mitochondria play a crucial role in adipocyte and immune cell functions. In fact, mitochondrial dysregulation is a common finding in a number of diseases that exhibit sex differences. It is, therefore, possible that mitochondria carry out sex-dimorphic functions. Prohibitin, an evolutionarily conserved pleiotropic protein, known to function as a mitochondrial chaperone, has multifaceted relationship with sex steroids and their receptors. New evidence indicates that prohibitin has roles in sex differences in multiple cell and tissue types, including adipocytes, macrophages, and dendritic cells. Transgenic mice overexpressing prohibitin in adipocytes, macrophages, and dendritic cells exhibit sex differences in metabolic and immune phenotypes, mediated through mitochondrial and plasma membrane signaling functions of prohibitin. Thus, the discovery of prohibitin as mediating the effects of sex steroids in multiple cell types has opened a new research direction to study the relationship between sex steroids and mitochondrial proteins and their impact on sex differences in health and disease. In this opinion article, we will provide a personal perspective of the role of prohibitin with cellular compartment- and tissue-specific functions in mediating sex-dimorphic adipose and immune functions. We believe that prohibitin is a potential target for sex-based new therapeutics for metabolic and immune diseases. Impact statement Traditional sex-related biases in research are now obsolete, and it is important to identify the sex of humans, animals, and even cells in research protocols, due to the role of sex as a fundamental facet of biology, predisposition to disease, and response to therapy. Genetic sex, epigenetics and hormonal regulations, generate sex-dimorphisms. Recent investigations acknowledge sex differences in metabolic and immune health as well as chronic diseases. Prohibitin, an evolutionarily conserved molecule, has pleotropic functions in mitochondrial housekeeping, plasma membrane signaling, and nuclear genetic transcription. Studies in adipocytes, macrophages, and transgenic mice indicate that prohibitin interacts with sex steroids and plays a role in mediating sex differences in adipose tissues and immune cell types. Prohibitin may, depending on context, modulate predisposition to chronic metabolic diseases and malignancy and, because of these attributes, could be a target for sex-based therapies of metabolic and immune-related diseases as well as cancer.

scholarly journals Tribbles in normal and malignant haematopoiesis

2015 ◽  
Vol 43 (5) ◽  
pp. 1112-1115 ◽  
Author(s):  
Sarah J. Stein ◽  
Ethan A. Mack ◽  
Kelly S. Rome ◽  
Warren S. Pear
Keyword(s):  
E3 Ligase ◽  
Cell Types ◽  
Protein Family ◽  
Conserved Motifs ◽  
Tissue Specific ◽  
Cellular Events ◽  
Haematopoietic Cells ◽  
Evolutionarily Conserved ◽  
Multiple Cell

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types.

The role of SLAM family receptors in immune cell signalingThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 832-843 ◽  
Author(s):  
Elena A. Ostrakhovitch ◽  
Shawn S.-C. Li
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Types ◽  
Health And Disease ◽  
Slam Family ◽  
Different Cell Types ◽  
Selection Of

The signaling lymphocyte-activating molecule (SLAM) family immunoreceptors are expressed in a wide array of immune cells, including both T and B lymphocytes. By virtue of their ability to transduce tyrosine phosphorylation signals through the so-called ITSM (immunoreceptor tyrosine-based switch motif) sequences, they play an important part in regulating both innate and adaptive immune responses. The critical role of the SLAM immunoreceptors in mediating normal immune reactions was highlighted in recent findings that SAP, a SLAM-associated protein, modulates the activities of various immune cells through interactions with different members of the SLAM family expressed in these cells. Importantly, mutations or deletions of the sap gene in humans result in the X-linked lymphoproliferative syndrome. In this review, we summarize current knowledge and survey the latest developments in signal transduction events triggered by the activation of SLAM family receptors in different cell types.

scholarly journals The Role of Exosomes in Bone Remodeling: Implications for Bone Physiology and Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Christos Masaoutis ◽  
Stamatios Theocharis
Keyword(s):  
Bone Remodeling ◽  
Current Knowledge ◽  
Active Role ◽  
Cell Types ◽  
Matrix Mineralization ◽  
Physiological Phenomenon ◽  
Health And Disease ◽  
Multiple Cell ◽  
Bone Physiology

Bone remodeling represents a physiological phenomenon of continuous bone tissue renewal that requires fine orchestration of multiple cell types, which is critical for the understanding of bone disease but not yet clarified in precise detail. Exosomes, which are cell-secreted nanovesicles drawing increasing attention for their broad biosignaling functions, can shed new light on how multiple heterogeneous cells communicate for the purpose of bone remodeling. In the healthy bone, exosomes transmit signals favoring both bone synthesis and resorption, regulating the differentiation, recruitment, and activity of most cell types involved in bone remodeling and even assuming an active role in extracellular matrix mineralization. Additionally, in the ailing bone, they actively participate in pathogenic processes constituting also potential therapeutic agents and drug vectors. The present review summarizes the current knowledge on bone exosomes and bone remodeling in health and disease.

scholarly journals MicroRNAs: Promising New Antiangiogenic Targets in Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sandra Gallach ◽  
Silvia Calabuig-Fariñas ◽  
Eloisa Jantus-Lewintre ◽  
Carlos Camps
Keyword(s):  
Cell Types ◽  
Biological Processes ◽  
Tumour Angiogenesis ◽  
Proliferation And Apoptosis ◽  
Sequence Complementarity ◽  
Specific Proteins ◽  
Health And Disease ◽  
Multiple Cell ◽  
Non Coding Rnas

MicroRNAs are one class of small, endogenous, non-coding RNAs that are approximately 22 nucleotides in length; they are very numerous, have been phylogenetically conserved, and involved in biological processes such as development, differentiation, cell proliferation, and apoptosis. MicroRNAs contribute to modulating the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules and so they play a key role in both health and disease. Angiogenesis is the process of new blood vessel formation from preexisting ones, which is particularly relevant to cancer and its progression. Over the last few years, microRNAs have emerged as critical regulators of signalling pathways in multiple cell types including endothelial and perivascular cells. This review summarises the role of miRNAs in tumour angiogenesis and their potential implications as therapeutic targets in cancer.

scholarly journals Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

2016 ◽  
Vol 113 (34) ◽  
pp. E4995-E5004 ◽  
Author(s):  
Wen Lu ◽  
Michael Winding ◽  
Margot Lakonishok ◽  
Jill Wildonger ◽  
Vladimir I. Gelfand
Keyword(s):  
Cytoplasmic Streaming ◽  
Cell Types ◽  
Nurse Cells ◽  
Wild Type ◽  
Actin Cortex ◽  
Microtubule Motor ◽  
Multiple Cell ◽  
Cytoplasmic Microtubules ◽  
Two Populations

Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants.

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

2018 ◽  
Vol 8 (9) ◽  
pp. 163 ◽  
Author(s):  
Caroline Gurvich ◽  
Kate Hoy ◽  
Natalie Thomas ◽  
Jayashri Kulkarni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Functioning ◽  
Sex Hormones ◽  
Reproductive Function ◽  
Health And Disease ◽  
And Function ◽  
The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

Sign in / Sign up

Export Citation Format

Share Document