The Swi3 protein plays a unique role in regulating respiration in eukaryotes

Swi3 is a key component of the well-known SWI–SNF chromatin remodelling complex. Here, we discovered a novel Swi3 function: Swi3 and its mammalian homologues suppress oxygen consumption, and Swi3 regulates the expression of aerobic respiration genes in an oxygen-dependent manner.

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Nuclear trafficking dynamics of Bromodomain-containing protein 7 (BRD7), a switch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complex subunit, in porcine oocytes and cleavage-stage embryos

Reproduction Fertility and Development ◽

10.1071/rd19030 ◽

2019 ◽

Vol 31 (9) ◽

pp. 1497

Author(s):

Jennifer S. Crodian ◽

Bethany M. Weldon ◽

Yu-Chun Tseng ◽

Birgit Cabot ◽

Ryan Cabot

Keyword(s):

Nuclear Export ◽

Chromosome Region ◽

Chromatin Remodelling ◽

Dominant Negative ◽

Dependent Manner ◽

Nuclear Trafficking ◽

Chromatin Remodelling Complex ◽

Unique Role ◽

A Subunit ◽

Cellular Compartments

In the work presented here, we investigated how bromodomain-containing protein 7 (BRD7), a subunit associated with switch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complexes, is trafficked between cellular compartments during embryo development. SWI/SNF complexes are multi-subunit complexes that contain a core catalytic subunit (SWI/SNF related, Matrix associated, Actin dependent Regulator of Chromatin, subfamily A, member 4, or member 2; SMARCA4 or SMARCA2) and a collection of additional subunits that guide the complexes to their appropriate loci; BRD7 is one of these additional subunits. We hypothesised that BRD7 is exported from the nuclei of porcine oocytes and embryos in a Chromosome Region Maintenance 1 (CRM1)-dependent manner and imported into the nuclei using the karyopherin α/β1 heterodimer. Porcine oocytes and embryos were treated with inhibitors of CRM1-mediated nuclear export and karyopherin α/β1-mediated nuclear import to test this hypothesis. An RNA interference assay and a dominant negative overexpression assay were also performed to determine if karyopherin α7 serves a specific role in BRD7 trafficking. Our findings indicate that BRD7 shuttles between nuclear and cytoplasmic compartments during cleavage development. The shuttling of BRD7 indicates that it serves a unique role in remodelling chromatin during this developmental window.

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Cell-type-dependent repression of yeast a-specific genes requires Itc1p, a subunit of the Isw2p–Itc1p chromatin remodelling complex

Microbiology ◽

10.1099/mic.0.25920-0 ◽

2003 ◽

Vol 149 (2) ◽

pp. 341-351 ◽

Cited By ~ 32

Author(s):

Cristina Ruiz ◽

Victoria Escribano ◽

Eulalia Morgado ◽

María Molina ◽

María J. Mazón

Keyword(s):

Chromatin Remodelling ◽

Cell Type ◽

Chromatin Remodelling Complex ◽

A Subunit

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BRM: the core ATPase subunit of SWI/SNF chromatin-remodelling complex—a tumour suppressor or tumour-promoting factor?

Epigenetics & Chromatin ◽

10.1186/s13072-019-0315-4 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Iga Jancewicz ◽

Janusz A. Siedlecki ◽

Tomasz J. Sarnowski ◽

Elzbieta Sarnowska

Keyword(s):

Synthetic Lethality ◽

Susceptibility Gene ◽

Chromatin Remodelling ◽

Tumour Suppressor ◽

Disease Stage ◽

Cancer Type ◽

Missense Mutations ◽

Loss Of Function ◽

Atpase Subunit ◽

Chromatin Remodelling Complex

Abstract BRM (BRAHMA) is a core, SWI2/SNF2-type ATPase subunit of SWI/SNF chromatin-remodelling complex (CRC) involved in various important regulatory processes including development. Mutations in SMARCA2, a BRM-encoding gene as well as overexpression or epigenetic silencing were found in various human diseases including cancer. Missense mutations in SMARCA2 gene were recently connected with occurrence of Nicolaides–Baraitser genetics syndrome. By contrast, SMARCA2 duplication rather than mutations is characteristic for Coffin–Siris syndrome. It is believed that BRM usually acts as a tumour suppressor or a tumour susceptibility gene. However, other studies provided evidence that BRM function may differ depending on the cancer type and the disease stage, where BRM may play a role in the disease progression. The existence of alternative splicing forms of SMARCA2 gene, leading to appearance of truncated functional, loss of function or gain-of-function forms of BRM protein suggest a far more complicated mode of BRM-containing SWI/SNF CRCs actions. Therefore, the summary of recent knowledge regarding BRM alteration in various types of cancer and highlighting of differences and commonalities between BRM and BRG1, another SWI2/SNF2 type ATPase, will lead to better understanding of SWI/SNF CRCs function in cancer development/progression. BRM has been recently proposed as an attractive target for various anticancer therapies including the use of small molecule inhibitors, synthetic lethality induction or proteolysis-targeting chimera (PROTAC). However, such attempts have some limitations and may lead to severe side effects given the homology of BRM ATPase domain to other ATPases, as well as due to the tissue-specific appearance of BRM- and BRG1-containing SWI/SNF CRC classes. Thus, a better insight into BRM-containing SWI/SNF CRCs function in human tissues and cancers is clearly required to provide a solid basis for establishment of new safe anticancer therapies.

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Acute inhibition of respiratory capacity of muscle reduces peak oxygen consumption

AJP Cell Physiology ◽

10.1152/ajpcell.1990.259.6.c889 ◽

1990 ◽

Vol 259 (6) ◽

pp. C889-C896 ◽

Cited By ~ 61

Author(s):

R. M. McAllister ◽

R. L. Terjung

Keyword(s):

Oxygen Consumption ◽

Electron Transport ◽

Cytochrome C ◽

Peak Oxygen Consumption ◽

Dependent Manner ◽

Cytochrome C Reductase ◽

Energy Demands ◽

Hindlimb Muscle ◽

Nadh Cytochrome

Electron transport capacity of skeletal muscle was inhibited in situ in an acute dose-dependent manner with myxothiazol, a tight-binding inhibitor of ubiquinone-cytochrome c reductase, complex III of the respiratory chain. Peak oxygen consumption of rat hindlimb muscle was determined via consecutive 10-min isometric contraction (100 ms at 100 Hz) periods of increasing energy demands (4, 8, 15, 30, 45, and 60 tetani/min), using an isolated hindlimb preparation perfused with a high oxygen delivery (approximately 6-8 mumol.min-1.g-1). Peak oxygen consumption decreased from 4.61 +/- 0.19 mumol.min-1.g-1 (control) in a dose-dependent manner to 0.73 +/- 0.07 mumol.min-1.g-1 at 0.50 microM myxothiazol in blood. Oxygen extraction decreased from 65 to 12% of delivered oxygen. Furthermore, the reduction in peak respiratory rate became evident at lower energy demands of the contraction sequence. Myxothiazol inhibition of respiration was not dependent on the presence of muscle contractions but was evident when mitochondria were uncoupled with carbonyl cyanide m-chlorophenylhydrazone. A 50% effective dosage (ED50) of 0.21 microM myxothiazol for inhibition of peak oxygen consumption closely resembled the inhibition of NADH-cytochrome c reductase activity (ED50 of 0.27 microM) determined from homogenates of the same muscles. This suggests that the peak oxygen consumption of skeletal muscle is tightly coupled to the capacity for electron transport evaluated by flux through NADH-cytochrome c reductase. If the enzyme activity measured in vitro correctly represents available enzymatic capacity within contracting muscle, approximately 75% of electron transport capacity for handling reducing equivalents generated from NADH is utilized during peak oxygen consumption of rat hindlimb muscle contracting in situ.

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The role of the SWI/SNF chromatin remodelling complex in the response to DNA double strand breaks

DNA Repair ◽

10.1016/j.dnarep.2020.102919 ◽

2020 ◽

Vol 93 ◽

pp. 102919

Author(s):

Alison Harrod ◽

Karen A. Lane ◽

Jessica A. Downs

Keyword(s):

Chromatin Remodelling ◽

Double Strand Breaks ◽

Dna Double Strand Breaks ◽

Chromatin Remodelling Complex ◽

Strand Breaks

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The Chromatin Remodelling Complex B-WICH Changes the Chromatin Structure and Recruits Histone Acetyl-Transferases to Active rRNA Genes

PLoS ONE ◽

10.1371/journal.pone.0019184 ◽

2011 ◽

Vol 6 (4) ◽

pp. e19184 ◽

Cited By ~ 34

Author(s):

Anna Vintermist ◽

Stefanie Böhm ◽

Fatemeh Sadeghifar ◽

Emilie Louvet ◽

Anethe Mansén ◽

...

Keyword(s):

Chromatin Structure ◽

Chromatin Remodelling ◽

Rrna Genes ◽

Chromatin Remodelling Complex

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The SWI/SNF chromatin remodelling complex: Its role in maintaining genome stability and preventing tumourigenesis

DNA Repair ◽

10.1016/j.dnarep.2015.04.023 ◽

2015 ◽

Vol 32 ◽

pp. 127-133 ◽

Cited By ~ 54

Author(s):

Peter M. Brownlee ◽

Cornelia Meisenberg ◽

Jessica A. Downs

Keyword(s):

Genome Stability ◽

Chromatin Remodelling ◽

Chromatin Remodelling Complex

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Palmitic acid acutely inhibits acetylcholine- but not GLP-1-stimulated insulin secretion in mouse pancreatic islets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00072.2010 ◽

2010 ◽

Vol 299 (3) ◽

pp. E475-E485 ◽

Cited By ~ 16

Author(s):

Nicolai M. Doliba ◽

Wei Qin ◽

Sergei A. Vinogradov ◽

David F. Wilson ◽

Franz M. Matschinsky

Keyword(s):

Fatty Acids ◽

Oxygen Consumption ◽

Insulin Secretion ◽

Insulin Release ◽

Cell Function ◽

Hormone Secretion ◽

Albumin Concentration ◽

Dependent Manner ◽

Fixed Concentration ◽

Stimulation Of

Fatty acids, acetylcholine, and GLP-1 enhance insulin secretion in a glucose-dependent manner. However, the interplay between glucose, fatty acids, and the neuroendocrine regulators of insulin secretion is not well understood. Therefore, we studied the acute effects of PA (alone or in combination with glucose, acetylcholine, or GLP-1) on isolated cultured mouse islets. Two different sets of experiments were designed. In one, a fixed concentration of 0.5 mM of PA bound to 0.15 mM BSA was used; in the other, a PA ramp from 0 to 0.5 mM was applied at a fixed albumin concentration of 0.15 mM so that the molar PA/BSA ratio changed within the physiological range. At a fixed concentration of 0.5 mM, PA markedly inhibited acetylcholine-stimulated insulin release, the rise of intracellular Ca2+, and enhancement of cAMP production but did not influence the effects of GLP-1 on these parameters of islet cell function. 2-ADB, an IP3 receptor inhibitor, reduced the effect of acetylcholine on insulin secretion and reversed the effect of PA on acetylcholine-stimulated insulin release. Islet perfusion for 35–40 min with 0.5 mM PA significantly reduced the calcium storage capacity of ER measured by the thapsigargin-induced Ca2+ release. Oxygen consumption due to low but not high glucose was reduced by PA. When a PA ramp from 0 to 0.5 mM was applied in the presence of 8 mM glucose, PA at concentrations as low as 50 μM significantly augmented glucose-stimulated insulin release and markedly reduced acetylcholine's effects on hormone secretion. We thus demonstrate that PA acutely reduces the total oxygen consumption response to glucose, glucose-dependent acetylcholine stimulation of insulin release, Ca2+, and cAMP metabolism, whereas GLP-1's actions on these parameters remain unaffected or potentiated. We speculate that acute emptying of the ER calcium by PA results in decreased glucose stimulation of respiration and acetylcholine potentiation of insulin secretion.

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Extracellular ATP inhibits transport in medullary thick ascending limbs: role of P2X receptors

AJP Renal Physiology ◽

10.1152/ajprenal.00325.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. F1168-F1173 ◽

Cited By ~ 25

Author(s):

Guillermo B. Silva ◽

Jeffrey L. Garvin

Keyword(s):

Nitric Oxide ◽

Oxygen Consumption ◽

Oxidative Phosphorylation ◽

Receptor Antagonist ◽

P2x Receptors ◽

Extracellular Atp ◽

Thick Ascending Limb ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Nitric Oxide Synthase Inhibitor

Absorption of NaCl by the thick ascending limb (TAL) involves active transport and therefore depends on oxidative phosphorylation. Extracellular ATP has pleiotropic effects, including both stimulation and inhibition of transport and inhibition of oxidative phosphorylation. However, it is unclear whether ATP alters TAL transport and how this occurs. We hypothesized that ATP inhibits TAL Na absorption by reducing Na entry. We measured oxygen consumption in TAL suspensions. ATP reduced oxygen consumption in a concentration-dependent manner. The purinergic (P2) receptor antagonist suramin (300 μM) blocked the effect of ATP on TAL oxygen consumption (147 ± 15 vs. 146 ± 16 nmol O2·min−1·mg protein−1). In contrast, the adenosine receptor antagonist theophylline did not block the effect of ATP on oxygen consumption. When Na-K-2Cl cotransport and Na/H exchange were blocked with furosemide (100 μM) plus dimethyl amiloride (100 μM), ATP did not inhibit TAL oxygen consumption (from 78 ± 13 to 98 ± 5 nmol O2·min−1·mg protein−1). The Na ionophore nystatin (200 U/ml) increased TAL oxygen consumption to a similar extent in both ATP- and vehicle-treated samples (368 ± 41 vs. 397 ± 47 nmol O2·min−1·mg protein−1). The nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (3 mM) blocked the ATP effects on TAL oxygen consumption (157 ± 10 vs. 165 ± 15 nmol O2·min−1·mg protein−1). The P2X-selective receptor antagonist NF023 blocked the effect of ATP on oxygen consumption, whereas the P2X-selective agonist β-γ-Me-ATP reduced oxygen consumption in a concentration-dependent manner. We conclude that ATP inhibits Na transport-related oxygen consumption in TALs by reducing Na entry and P2X receptors and nitric oxide mediate this effect.

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