K<sub>v</sub>1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress

Fountain, Samuel J.; Cheong, Alex; Li, Jing; Döndaş, Naciye Yaktubay; Zeng, Fanning; Wood, Ian C.; Beech, David J.

doi:10.1152/ajpheart.00637.2007

Cited by 24 publications

(18 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hormones and other second messengers modulate the transcription of multiple ion channel genes, including those encoding the voltage-gated K ϩ channels Kv4.2 and Kv1.5 (12,15,31) and the BK channel-encoding mouse slo gene (20). Whereas many of these channel genes contain hormone response elements within the promoter, others contain transcription factor binding sites that either complement these elements or provide hormone responsiveness themselves.…”

Section: Discussionmentioning

confidence: 99%

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

Pierce

England

2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Overexpression of the small-conductance calcium-activated K(+) channel 3 (SK3) in transgenic mice compromises parturition, suggesting that the SK3 channel plays a role in pregnancy. In wild-type mouse myometrium, expression of SK3 transcript and protein is significantly reduced during pregnancy, but the mechanism(s) responsible for this attenuation of channel expression is unknown. The promoter region of the SK3-encoding mouse KCNN3 gene contains two binding sites for specificity protein (Sp) transcription factors, two of which are expressed in the uterus: Sp1, which enhances gene transcription in response to estrogen; and Sp3, which competes for the same binding motif as Sp1 and can repress gene expression. We investigated the hypothesis that Sp1 and Sp3 regulate SK3 channel expression during pregnancy. In mouse myometrium, Sp1 expression was reduced during late gestation, whereas Sp3 expression levels were constant throughout pregnancy. Using a reporter system, we found that Sp1 overexpression resulted in a significant increase in SK3 promoter activation and that Sp3 cotransfection reduced promoter activation to basal levels. These findings indicate that Sp3 outcompetes Sp1 to decrease SK3 transcription. To determine whether high levels of estrogen in vivo can affect the regulation of SK3 protein levels by Sp factors, ovariectomized mice were implanted with a 17β-estradiol or placebo pellet for 3 wk; estrogen-treated mice had reduced uterine SK3 protein expression compared with placebo-treated counterparts. In human myometrial cells overexpressing Sp1, estrogen treatment stimulated expression of the SK3 transcript. Overall, our findings indicate that Sp1 and Sp3 compete to regulate SK3 channel expression during pregnancy in response to stimulation by estrogen.

show abstract

Section: Discussionmentioning

confidence: 99%

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

Pierce

England

2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…In this regard, ANG II has been reported to directly inhibit K V channel activity by activation of protein kinase C (PKC)⑀ and inhibition of protein kinase A (PKA) (29). Additionally, gene expression of ␣ 1.5 is regulated by the Sp1 transcription factor that is sensitive to oxidative stress (12,22), a feature of hypertension that has been partially attributed to ANG II (45,47). Although the signaling molecules in VSMCs that link elevated ANG II to K V 1 channel suppression are unclear, our findings suggest that the reduced expression of even a single mRNA coding for either ␣ 1.2 or ␣ 1.5 may limit their optimal coassembly into K V 1 channel heterotetramers, resulting in a sparse expression of functional K V 1 channels on the VSMC surface.…”

Section: Discussionmentioning

confidence: 99%

Loss of cerebrovascular Shaker-type K⁺ channels: a shared vasodilator defect of genetic and renal hypertensive rats

Tobin¹,

Joseph²,

Al‐Kindi³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The cerebral arteries of hypertensive rats are depolarized and highly myogenic, suggesting a loss of K(+) channels in the vascular smooth muscle cells (VSMCs). The present study evaluated whether the dilator function of the prominent Shaker-type voltage-gated K(+) (K(V)1) channels is attenuated in middle cerebral arteries from two rat models of hypertension. Block of K(V)1 channels by correolide (1 micromol/l) or psora-4 (100 nmol/l) reduced the resting diameter of pressurized (80 mmHg) cerebral arteries from normotensive rats by an average of 28 +/- 3% or 26 +/- 3%, respectively. In contrast, arteries from spontaneously hypertensive rats (SHR) and aortic-banded (Ao-B) rats with chronic hypertension showed enhanced Ca(2+)-dependent tone and failed to significantly constrict to correolide or psora-4, implying a loss of K(V)1 channel-mediated vasodilation. Patch-clamp studies in the VSMCs of SHR confirmed that the peak K(+) current density attributed to K(V)1 channels averaged only 5.47 +/- 1.03 pA/pF, compared with 9.58 +/- 0.82 pA/pF in VSMCs of control Wistar-Kyoto rats. Subsequently, Western blots revealed a 49 +/- 7% to 66 +/- 7% loss of the pore-forming alpha(1.2)- and alpha(1.5)-subunits that compose K(V)1 channels in cerebral arteries of SHR and Ao-B rats compared with control animals. In each case, the deficiency of K(V)1 channels was associated with reduced mRNA levels encoding either or both alpha-subunits. Collectively, these findings demonstrate that a deficit of alpha(1.2)- and alpha(1.5)-subunits results in a reduced contribution of K(V)1 channels to the resting diameters of cerebral arteries from two rat models of hypertension that originate from different etiologies.

show abstract

“…K v channel function is also sensitive to hypercholesterolemia 183, 184 , and to pathophysiologically relevant concentrations of ROS in both animals and humans 185 . Elevated levels of ROS in CAD and its associated risk factors decrease expression of K v channels in animals 186, 187 possibly by down-regulating the transcription factor Sp1 188 .…”

Section: Role Of Vsmc In the Regulation Of Human Arteriolar Tonementioning

confidence: 99%

The Human Microcirculation

Gutterman

Chabowski

Kadlec

et al. 2016

Circulation Research

241

141

View full text Add to dashboard Cite

The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation, the microvasculature plays a critical role in modulating vascular tone by endothelial release of an unusually diverse family of compounds including nitric oxide, other reactive oxygen species, and arachidonic acid metabolites. Animal models have provided excellent insight into mechanisms of vasoregulation in health and disease. However there are unique aspects of the human microcirculation that serve as the focus of this review. The concept is put forth that vasculo-parenchymal communication is multimodal, with vascular release of nitric oxide eliciting dilation and preserving normal parenchymal function by inhibiting inflammation and proliferation. Likewise, in disease or stress, endothelial release of ROS both mediates dilation and parenchymal inflammation leading to cellular dysfunction, thrombosis, and fibrosis. Some pathways responsible for this stress-induced shift in mediator of vasodilation are proposed. This paradigm may help explain why microvascular dysfunction is such a powerful predictor of cardiovascular events, and help identify new approaches to treatment and prevention.

show abstract

K_v1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress

Abstract: Fountain SJ, Cheong A, Li J, Dondas NY, Zeng F, Wood IC, Beech DJ. Kv1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress.

Cited by 24 publications

References 52 publications

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

Loss of cerebrovascular Shaker-type K⁺ channels: a shared vasodilator defect of genetic and renal hypertensive rats

The Human Microcirculation

Contact Info

Product

Resources

About

Kv1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress

Abstract: Fountain SJ, Cheong A, Li J, Dondas NY, Zeng F, Wood IC, Beech DJ. Kv1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress.

Cited by 24 publications

References 52 publications

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

SK3 channel expression during pregnancy is regulated through estrogen and Sp factor-mediated transcriptional control of theKCNN3gene

Loss of cerebrovascular Shaker-type K+ channels: a shared vasodilator defect of genetic and renal hypertensive rats

The Human Microcirculation

Contact Info

Product

Resources

About

K_v1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress

Loss of cerebrovascular Shaker-type K⁺ channels: a shared vasodilator defect of genetic and renal hypertensive rats