Regulation of connexin expression by transcription factors and epigenetic mechanisms

Oyamada, Masahito; Takebe, Kumiko; Oyamada, Yumiko

doi:10.1016/j.bbamem.2011.12.031

Cited by 104 publications

(88 citation statements)

References 143 publications

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“…Mpp7 appears involved in epithelial tight junction formation (Xiao et al 2012), although again, no close cochlear link has been described. Gjd4 encodes a gap junctional component (Cx39) that has not been described in the cochlea (Oyamada et al 2013). Once again, if allelic similarity between B6, BALB, and CBA/J provides a guide, we may suspect genes that are similar between BALB and CBA/J, and polymorphic between these strains and B6.…”

Section: Chromosome 18mentioning

confidence: 99%

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

Ohlemiller

Kiener

Gagnon

2016

JARO

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We reported earlier that the endocochlear potential (EP) differs between C57BL/6J (B6) and BALB/cJ (BALB) mice, being lower in BALBs by about 10 mV (Ohlemiller et al. Hear Res 220: 10-26, 2006). This difference corresponds to strain differences with respect to the density of marginal cells in cochlear stria vascularis. After about 1 year of age, BALB mice also tend toward EP reduction that correlates with further marginal cell loss. We therefore suggested that early sub-clinical features of the BALB stria vascularis may predispose these mice to a condition modeling Schuknecht's strial presbycusis. We further reported (Ohlemiller et al. J Assoc Res Otolaryngol 12: 45-58, 2011) that the acute effects of a 2-h 110 dB SPL noise exposure differ between B6 and BALB mice, such that the EP remains unchanged in B6 mice, but is reduced by 40-50 mV in BALBs. In about 25 % of BALBs, the EP does not completely recover, so that permanent EP reduction may contribute to noise-induced permanent threshold shifts in BALBs. To identify genes and alleles that may promote natural EP variation as well as noiserelated EP reduction in BALB mice, we have mapped related quantitative trait loci (QTLs) using 12 recombinant inbred (RI) strains formed from B6 and BALB (CxB1-CxB12). EP and strial marginal cell density were measured in B6 mice, BALB mice, their F1 hybrids, and RI mice without noise exposure, and 1-3 h after broadband noise (4-45 kHz, 110 dB SPL, 2 h). For unexposed mice, the strain distribution patterns for EP and marginal cell density were used to generate preliminary QTL maps for both EP and marginal cell density. Six QTL regions were at least statistically suggestive, including a significant QTL for marginal cell density on chromosome 12 that overlapped a weak QTL for EP variation. This region, termed Maced (Marginal cell density QTL) supports the notion of marginal cell density as a genetically influenced contributor to natural EP variation. Candidate genes for Maced notably include Foxg1, Foxa1, Akap6, Nkx2-1, and Pax9. Noise exposure produced significant EP reductions in two RI strains as well as significant EP increases in two RI strains. QTL mapping of the EP in noise-exposed RI mice yielded four suggestive regions. Two of these overlapped with QTL regions we previously identified for noise-related EP reduction in CBA/J mice (Ohlemiller et al. Hear Res 260: 47-53, 2010) on chromosomes 5 and 18 (Nirep). The present map may narrow the Nirep interval to a~10-Mb region of proximal Chr. 18 that includes Zeb1, Arhgap12, Mpp7, and Gjd4. This study marks the first exploration of natural gene variants that modulate the EP. Their orthologs may underlie some human hearing loss that originates in the lateral wall.Electronic supplementary material The online version of this article

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Section: Chromosome 18mentioning

confidence: 99%

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

Ohlemiller

Kiener

Gagnon

2016

JARO

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“…The transcription of Cx43 is controlled by homebox factors including Nxk2.5 and Irx3 [66,67]. Posttranslational modification regulates channel assembly, trafficking, gating, internalization, and protein degradation.…”

Section: Modulation Of Gap Junction Channel Functionmentioning

confidence: 99%

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Magyar

Bányász

Szentandrássy

et al. 2014

CPD

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The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling.Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR.Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

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“…Moreover, a plethora of studies has demonstrated that connexin expression can be modulated at different post-transcriptional steps, although regulation of connexin gene transcription is accepted as an important mechanism in controlling the temporal pattern and amount of connexin protein needed for GJIC. Agents such as steroid hormones and cytokines are well known to upregulate cell-type nonspecific or specific transcription factors required for connexin gene transcription in different organs (for review, see Oyamada et al (2013)). Regulation of the different connexins plays a significant role in embryogenesis, cell proliferation, apoptosis, migration and differentiation (Haass et al 2004, Levin 2007, Aasen 2014, Carette et al 2014.…”

Section: Introductionmentioning

confidence: 99%

Physiological roles of connexins in labour and lactation

Kidder

Winterhager

2015

Reproduction

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The connexin family of proteins are best known as oligomerizing to form intercellular membrane channels (gap junctions) that metabolically and ionically couple cells to allow for coordinated cellular function. Nowhere in the body is this role better illustrated than in the uterine smooth muscle during parturition, where gap junctions conduct the contraction wave throughout the tissue to deliver the baby. Parturition is followed by the onset of lactation with connexins contributing to both the dramatic reorganization of mammary gland tissue leading up to lactation and the smooth muscle contraction of the myoepithelial cells which extrudes the milk. This review summarizes what is known about the expression and roles of individual connexin family members in the uterus during labour and in the mammary glands during development and lactation. Connexin loss or malfunction in mammary glands and the uterus can have serious implications for the health of both the mother and the newborn baby.Reproduction (2015) 150 R129-R136

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Regulation of connexin expression by transcription factors and epigenetic mechanisms

Cited by 104 publications

References 143 publications

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Physiological roles of connexins in labour and lactation

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