Zn2+-transporters ZIP7 and ZnT7 play important role in progression of cardiac dysfunction via affecting sarco(endo)plasmic reticulum-mitochondria coupling in hyperglycemic cardiomyocytes

Tuncay, Erkan; Bitirim, Ceylan Verda; Olğar, Yusuf; Durak, Ayşegül; Rutter, Guy A.; Turan, Belma

doi:10.1016/j.mito.2017.12.011

Cited by 47 publications

(36 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been already demonstrated that there is a close relationship between increases in oxidative stress, at most, ROS and [Zn 2+ ] i in cardiomyocytes under pathological condition [26,37,39], while the marked increase in ROS was demonstrated in the aged cardiomyocytes. Therefore, here, we first determined the cellular [Zn 2+ ] i in the aged ventricular cardiomyocytes isolated from 24-month old rats.…”

Section: Resultsmentioning

confidence: 99%

“…The [Zn 2+ ] i -homeostasis and the suborganelle levels of [Zn 2+ ] are altered under pathological conditions, including hyperglycemia in cardiomyocytes [37,38]. Moreover, we have shown that a re-distribution of the expression level of some Zn 2+ -transporters can play an important contribution to those changes [37,39]. In the literature, there is a limited number of studies on the role of cellular [Zn 2+ ] and Zn 2+ -transporters in the aged heart function [40].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Olğar

Tuncay

Turan

2019

IJMS

Self Cite

View full text Add to dashboard Cite

Aging is an important risk factor for cardiac dysfunction. Heart during aging exhibits a depressed mechanical activity, at least, through mitochondria-originated increases in ROS. Previously, we also have shown a close relationship between increased ROS and cellular intracellular free Zn2+ ([Zn2+]i) in cardiomyocytes under pathological conditions as well as the contribution of some re-expressed levels of Zn2+-transporters for redistribution of [Zn2+]i among suborganelles. Therefore, we first examined the cellular (total) [Zn2+] and then determined the protein expression levels of Zn2+-transporters in freshly isolated ventricular cardiomyocytes from 24-month rat heart compared to those of 6-month rats. The [Zn2+]i in the aged-cardiomyocytes was increased, at most, due to increased ZIP7 and ZnT8 with decreased levels of ZIP8 and ZnT7. To examine redistribution of the cellular [Zn2+]i among suborganelles, such as Sarco/endoplasmic reticulum, S(E)R, and mitochondria ([Zn2+]SER and [Zn2+]Mit), a cell model (with galactose) to mimic the aged-cell in rat ventricular cell line H9c2 was used and demonstrated that there were significant increases in [Zn2+]Mit with decreases in [Zn2+]SER. In addition, the re-distribution of these Zn2+-transporters were markedly changed in mitochondria (increases in ZnT7 and ZnT8 with no changes in ZIP7 and ZIP8) and S(E)R (increase in ZIP7 and decrease in ZnT7 with no changes in both ZIP8 and ZnT8) both of them isolated from freshly isolated ventricular cardiomyocytes from aged-rats. Furthermore, we demonstrated that cellular levels of ROS, both total and mitochondrial lysine acetylation (K-Acetylation), and protein-thiol oxidation were significantly high in aged-cardiomyocytes from 24-month old rats. Using a mitochondrial-targeting antioxidant, MitoTEMPO (1 µM, 5-h incubation), we provided an important data associated with the role of mitochondrial-ROS production in the [Zn2+]i-dyshomeostasis of the ventricular cardiomyocytes from 24-month old rats. Overall, our present data, for the first time, demonstrated that a direct mitochondria-targeting antioxidant treatment can be a new therapeutic strategy during aging in the heart through a well-controlled [Zn2+] distribution among cytosol and suborganelles with altered expression levels of the Zn2+-transporters.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Olğar

Tuncay

Turan

2019

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, Estrada et al report a downregulation of STIM1 in coronary artery endothelial cells isolated from mice with streptozotocin‐induced diabetes 22 . Similarly, reduced STIM1 expression has been found in bladder SMCs of streptozozin‐induced diabetic rats at 12 weeks of age, 40 as well as in embryonic rat cardiomyocytes cultured for 24 hours in HG 41 and in pancreatic beta‐cells derived from diabetic patients or streptozozin‐treated mice 42 . Consistent with these data and with the observed reduction of SOCE amplitude in our assays, we show here that STIM1 mRNA expression is reduced in SMAs of ZDF rats, although protein expression in our experiments is comparable to control animals (Figure 5).…”

Section: Discussionmentioning

confidence: 93%

Reduced store‐operated Ca²⁺ entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats

Schach

Wester

Leibl

et al. 2020

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Diabetes is a major risk factor for cardiovascular disease, affecting both endothelial and smooth muscle cells. Store-operated Ca 2+ channels (SOCCs) have been implicated in many diabetic complications. Vascular dysfunction is common in patients with diabetes, but the role of SOCCs in diabetic vasculopathy is still unclear. Our research aimed to investigate the effects of high glucose (HG) on store-operated Ca 2+ entry (SOCE) in small arteries. Small mesenteric arteries from type 2 diabetic Zucker fatty rats (ZDF) versus their non-diabetic controls (Zucker lean, ZL) were examined in a pressurized myograph. Vascular smooth muscle cells (VSMC) were isolated and intracellular Ca 2+ was measured (Fura 2-AM). A specific protocol to deplete intracellular Ca 2+ stores and thereby open SOCCs, as well as pharmacological SOCE inhibitors (SKF-96365, BTP-2), were used to artificially activate and inhibit SOCE, respectively. High glucose (40 mmol/L) relaxed arteries in a SKF-sensitive manner.Diabetic arteries exhibited reduced HG-induced relaxation, as well as reduced contraction after Ca 2+ replenishment. Further, the rise in intracellular Ca 2+ on account of SOCE is diminished in diabetic versus non-diabetic VSMCs and was insensitive to HG in diabetic VSMCs. The expression of SOCC proteins was measured, detecting a downregulation of Orai1 in diabetes. In conclusion, diabetes leads to a reduction of SOCE and SOCE-induced contraction, which is unresponsive to HG-mediated inhibition. The reduced expression of Orai1 in diabetic arteries could account for the observed reduction in SOCE. K E Y W O R D Sdiabetes, high glucose, small mesenteric arteries, store-operated calcium entry, vascular smooth muscle, ZDF

show abstract

“…Zn 2+ transporter 7 (ZNT7), the linear parental gene of mmu_circ_0001160, has been shown to be associated with DM by interfering with insulin secretion ( 50 , 51 ). Furthermore, Tuncay et al ( 52 ) demonstrated that the novel role of ZNT7 in hyperglycemic cardiomyocytes by affecting sarco(endo)plasmic reticulum-mitochondria coupling. Based on the hypothesis that circRNAs may affect its linearly expressed gene, it was hypothesized that mmu_circ_0001160 may interfere with early-stage DCM by producing a ZNT7-related protein.…”

Section: Discussionmentioning

confidence: 99%

Expression profiling of circular RNAs and their potential role in early‑stage diabetic cardiomyopathy

Dong

et al. 2020

Mol Med Rep

View full text Add to dashboard Cite

diabetic cardiomyopathy (dcM) is a severe cardiovascular complication of diabetes mellitus (dM). detecting dcM during the early stages of the disease remains a challenge, as the molecular mechanisms underlying early-stage dcM are not clearly understood. circular rna (circrna), a type of non-coding RNA, has been confirmed to be associated with numerous diseases. However, it is still unclear how circrnas are involved in early-stage dcM. in the present study, heart tissues harvested from BKS-db/db knockout mice were identified through high-throughput rna sequencing technology. A total of 58 significantly differentially expressed circRNAs were identified in the db/db sample. Among these, six upregulated circRNAs and seven downregulated circRNAs were detected by reverse transcription-quantitative Pcr and analyzed using Gene ontology and Kyoto encyclopedia of Genes and Genomes. Furthermore, based on the predicted binding site with microRNAs (miRNAs) involved in DCM, five circrnas (mmu_circ_0000652, mmu_circ_0000547, mmu_ circ_0001058, mmu_circ_0000680 and novel_circ_0004285) were shown to serve as competing endogenous (ce)rnas. The corresponding mirnas and mrnas of the cernas were also verified, and two promising circRNA-miRNA-mRNA regulatory networks were determined. Finally, internal ribosome entry site prediction combined with open reading frame prediction indicated that it was highly possible that mmu_circ_0001160 encoded a protein. in the present study, a comprehensive analysis of the circRNA expression profile during the early phase of dcM was performed, and two promising circrna-mirna-mrna regulatory networks were identified. These results lay the foundation for unravelling the underlying pathogenesis of dcM, and highlight potential biomarkers and therapeutic targets for the treatment of dcM at an early stage.

show abstract

Zn2+-transporters ZIP7 and ZnT7 play important role in progression of cardiac dysfunction via affecting sarco(endo)plasmic reticulum-mitochondria coupling in hyperglycemic cardiomyocytes

Cited by 47 publications

References 61 publications

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Reduced store‐operated Ca²⁺ entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats

Expression profiling of circular RNAs and their potential role in early‑stage diabetic cardiomyopathy

Contact Info

Product

Resources

About

Zn2+-transporters ZIP7 and ZnT7 play important role in progression of cardiac dysfunction via affecting sarco(endo)plasmic reticulum-mitochondria coupling in hyperglycemic cardiomyocytes

Cited by 47 publications

References 61 publications

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Reduced store‐operated Ca2+ entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats

Expression profiling of circular RNAs and their potential role in early‑stage diabetic cardiomyopathy

Contact Info

Product

Resources

About

Reduced store‐operated Ca²⁺ entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats