Molecular mechanisms and physiological relevance of RGK proteins in the heart

2017 ◽  
Vol 222 (4) ◽  
pp. e13016 ◽  
Author(s):  
U. Meza ◽  
D. Beqollari ◽  
R. A. Bannister
Keyword(s):  
Molecular Mechanisms ◽  
Physiological Relevance ◽  
Rgk Proteins

scholarly journals Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization

2021 ◽  
Vol 12 ◽  
Author(s):  
Christopher A. Waker ◽  
Melissa R. Kaufman ◽  
Thomas L. Brown
Keyword(s):  
Mouse Models ◽  
Molecular Mechanisms ◽  
Human Condition ◽  
Definitive Treatment ◽  
Specific Gene ◽  
Adenoviral Infection ◽  
Physiological Relevance ◽  
Increased Risk ◽  
Therapeutic Development ◽  
Surgical Manipulation

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and include mixed mouse strain crosses, genetic overexpression and knockout, exogenous agent administration, surgical manipulation, systemic adenoviral infection, and trophoblast-specific gene transfer. These models have been useful to investigate how biological perturbations identified in human PE are involved in the generation of PE-like symptoms and have improved the understanding of the molecular mechanisms underpinning the human condition. However, these approaches were characterized by a wide variety of physiological endpoints, which can make it difficult to compare effects across models and many of these approaches have aspects that lack physiological relevance to this human disorder and may interfere with therapeutic development. This report provides a comprehensive review of mouse models that exhibit PE-like symptoms and a proposed standardization of physiological characteristics for analysis in murine models of PE.

scholarly journals Extracellular vesicles: Exosomes, microvesicles, and friends

2013 ◽  
Vol 200 (4) ◽  
pp. 373-383 ◽  
Author(s):  
Graça Raposo ◽  
Willem Stoorvogel
Keyword(s):  
Plasma Membrane ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Vesicle Release ◽  
Physiological Relevance ◽  
And Function ◽  
Extracellular Environment

Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.

Invited Review: Redox modulation of skeletal muscle contraction: what we know and what we don't

2001 ◽  
Vol 90 (2) ◽  
pp. 724-731 ◽  
Author(s):  
Michael B. Reid
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Controversial Issues ◽  
Skeletal Muscle Function ◽  
Skeletal Muscle Contraction ◽  
Physiological Relevance ◽  
Endogenous Regulators

Over the past decade, reactive oxygen species (ROS) and nitric oxide (NO) derivatives have been established as physiological modulators of skeletal muscle function. This mini-review addresses the roles of these molecules as endogenous regulators of muscle contraction. The article is organized in two parts. First, established concepts are briefly outlined. This section provides an overview of ROS production by muscle, antioxidant buffers that oppose ROS effects, enzymatic synthesis of NO in muscle, the effects of endogenous ROS on contractile function, and NO as a contractile modulator. Second, a selected group of unresolved topics are highlighted. These more controversial issues include putative source(s) of regulatory ROS, the relative importance of the two NO synthase isoforms constitutively coexpressed by muscle fibers, molecular mechanisms of ROS and NO action, and the physiological relevance of redox regulation. By discussing current questions, as well as the established paradigm, this article is intended to further debate and stimulate research in this area.

Membrane Fusion Induced by Phospholipase C and Sphingomyelinases

2000 ◽  
Vol 20 (6) ◽  
pp. 443-463 ◽  
Author(s):  
Félix M. Goñi ◽  
Alicia Alonso
Keyword(s):  
Experimental Evidence ◽  
Membrane Fusion ◽  
Phospholipase C ◽  
Molecular Mechanisms ◽  
Vesicle Fusion ◽  
Lipid Vesicle ◽  
The Past ◽  
Physiological Relevance

In the past decade lipid vesicle fusion induced by either bacterial PC-preferring phospholipase C, phosphatidylinositol-specific phospholipase C, sphingomyelinase, or a combination of phospholipase C and sphingomyelinase has been demonstrated. In the present paper, the experimental evidence is reviewed, and discussed in terms of the underlying molecular mechanisms of fusion, and of the possible physiological relevance of these findings.

scholarly journals p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shun Kageyama ◽  
Sigurdur Runar Gudmundsson ◽  
Yu-Shin Sou ◽  
Yoshinobu Ichimura ◽  
Naoki Tamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Oxidative Stress Response ◽  
Liquid Droplets ◽  
Autophagosome Formation ◽  
Selective Autophagy ◽  
Selective Degradation ◽  
Physiological Relevance ◽  
Related Proteins

AbstractAutophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.

The induction of Trypanosoma cruzi trypomastigote to amastigote transformation by low pH

Parasitology ◽  
1995 ◽  
Vol 110 (5) ◽  
pp. 547-554 ◽  
Author(s):  
S. Tomlinson ◽  
F. Vandekerckhove ◽  
U. Frevert ◽  
V. Nussenzweig
Keyword(s):  
Trypanosoma Cruzi ◽  
Molecular Mechanisms ◽  
Low Ph ◽  
Critical Stage ◽  
Intracellular Amastigotes ◽  
Electron Microscopical Analysis ◽  
Physiological Relevance ◽  
Electron Microscopical ◽  
Extracellular Amastigotes

SUMMARYFollowing cell invasion, Trypanosoma cruzi trypomastigotes transform into amastigotes, which are the mammalian replicative forms of the parasite. Although amastigotes represent a critical stage in the life-cycle of T. cruzi, little is known of the factors controlling trypomastigote to amastigote transformation. Kanbera et al. (1990) observed that exposure of trypomastigotes to acidic pH induced their transformation into rounded forms resembling amastigotes. We confirm their observation and, using two strains of T. cruzi, establish that these transformants are ultrastructurally and biochemically indistinguishable from natural amastigotes. Incubation of trypomastigotes in medium at pH 5·0 for 2 h was sufficient to trigger their transformation into forms resembling amastigotes. Electron microscopical analysis confirmed that the kinetoplast structure, and general morphological features of the acid-induced, extracellular amastigotes were indistinguishable from those of intracellular-derived amastigotes. The extracellular transformation was accompanied by the acquisition of the stage-specific surface antigen of the naturally transformed amastigotes (Ssp-4), and loss of a stagespecific trypomastigote antigen (Ssp-3). Trypomastigotes incubated at neutral pH did not transform into amastigotes, and did not acquire the Ssp-4 epitope or lose the Ssp-3 epitope. Finally, acid-induced amastigotes subsequently incorporated [3H]thymidine into their DNA, indicating that the important replicative property of intracellular amastigotes is also exhibited by these in vitro transformants. This effect of low pH appears to be of physiological relevance, and acid-induced extracellular transformation appears to represent a valid experimental technique for studies of the molecular mechanisms involved in the differentiation process.

scholarly journals Critical role of CRAG, a splicing variant of centaurin-γ3/AGAP3, in ELK1-dependent SRF activation at PML bodies

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shun Nagashima ◽  
Keisuke Takeda ◽  
Isshin Shiiba ◽  
Mizuho Higashi ◽  
Toshifumi Fukuda ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Critical Role ◽  
Developing Brain ◽  
Promyelocytic Leukaemia ◽  
Dependent Manner ◽  
Splicing Variant ◽  
Physiological Relevance ◽  
Pml Bodies

AbstractCRMP-5-associated GTPase (CRAG), a short splicing variant of centaurin-γ3/AGAP3, is predominantly expressed in the developing brain. We previously demonstrated that CRAG, but not centaurin-γ3, translocates to the nucleus and activates the serum response factor (SRF)-c-Fos pathway in cultured neuronal cells. However, the physiological relevance of CRAG in vivo is unknown. Here, we found that CRAG/centaurin-γ3–knockout mice showed intensively suppressed kainic acid-induced c-fos expression in the hippocampus. Analyses of molecular mechanisms underlying CRAG-mediated SRF activation revealed that CRAG has an essential role in GTPase activity, interacts with ELK1 (a co-activator of SRF), and activates SRF in an ELK1-dependent manner. Furthermore, CRAG and ELK1 interact with promyelocytic leukaemia bodies through SUMO-interacting motifs, which is required for SRF activation. These results suggest that CRAG plays a critical role in ELK1-dependent SRF-c-fos activation at promyelocytic leukaemia bodies in the developing brain.

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