Protein kinase C (PKC) mediated interaction between conexin43 (Cx43) and K+(ATP) channel subunit (Kir6.1) in cardiomyocyte mitochondria: Implications in cytoprotection against hypoxia induced cell apoptosis

Waza, Ajaz Ahmad; Andrabi, Khurshid Iqbal; Hussain, Mahboob Ul

doi:10.1016/j.cellsig.2014.05.002

Cited by 58 publications

(47 citation statements)

References 29 publications

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“…Adsorption assays in which the antibody was preincubated with the immunogenic peptide demonstrated the specificity of the polyclonal anti-PKA α-subunit [18]. Studies using antibodies obtained from the source we used reported only single bands in Western blots, where PKCα, PKCε, PKCλ or PKCζ were among the protein kinases of interest [19][20][21][22].…”

Section: Methodsmentioning

confidence: 99%

Altered signaling pathways linked to angiotensin II underpin the upregulation of renal Na+-ATPase in chronically undernourished rats

Silva

Muzi‐Filho

Pereira‐Acácio

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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This study has investigated the participation of altered signaling linked to angiotensin II (Ang II) that could be associated with increased Na(+) reabsorption in renal proximal tubules during chronic undernutrition. A multideficient chow for rats (basic regional diet, BRD) was used, which mimics several human diets widely taken in developing countries. The Vmax of the ouabain-resistant Na(+)-ATPase resident in the basolateral membranes increased >3-fold (P<0.001) accompanied by an increase in Na(+) affinity from 4.0 to 0.2mM (P<0.001). BRD rats had a >3-fold acceleration of the formation of phosphorylated intermediates in the early stage of the catalytic cycle (in the E1 conformation) (P<0.001). Immunostaining showed a huge increase in Ang II-positive cells in the cortical tubulointerstitium neighboring the basolateral membranes (>6-fold, P<0.001). PKC isoforms (α, ε, λ, ζ), Ang II type 1 receptors and PP2A were upregulated in BRD rats (in %): 55 (P<0.001); 35 (P<0.01); 125, 55, 11 and 30 (P<0.001). PKA was downregulated by 55% (P<0.001). With NetPhosK 1.0 and NetPhos 2.0, we detected 4 high-score (>0.70) regulatory phosphorylation sites for PKC and 1 for PKA in the primary sequence of the Na(+)-ATPase α-subunit, which are located in domains that are key for Na(+) binding and catalysis. Therefore, chronic undernutrition stimulates tubulointerstitial activity of Ang II and impairs PKC- and PKA-mediated regulatory phosphorylation, which culminates in an exaggerated Na(+) reabsorption across the proximal tubular epithelium.

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Section: Methodsmentioning

confidence: 99%

Altered signaling pathways linked to angiotensin II underpin the upregulation of renal Na+-ATPase in chronically undernourished rats

Silva

Muzi‐Filho

Pereira‐Acácio

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Indeed, the role of Cx43 in hypoxia has been well described in other cell types. For instance, Cx43 is a key mediator of cell protection during ischemia/hypoxia in cardiomyocytes (41).…”

Section: Discussionmentioning

confidence: 99%

The Selective Degradation of Synaptic Connexin 43 Protein by Hypoxia-induced Autophagy Impairs Natural Killer Cell-mediated Tumor Cell Killing

Tittarelli

Janji

Moer

et al. 2015

Journal of Biological Chemistry

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Background:The regulation of gap junction protein connexin 43 (Cx43), involved in natural killer (NK) cell-mediated tumor killing, is still elusive. Results: Hypoxia-induced autophagy selectively degrades gap junctional Cx43 from immune synapses and impairs NK-mediated melanoma cell lysis. Conclusion: A hypoxic microenvironment induces melanoma resistance to NK cells via modulation of Cx43 channels. Significance: Targeting autophagy prevents gap-junctional Cx43 degradation and potentiates NK-based tumor immunotherapies.

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“…To verify further that the effect of clusterin on cell death induced by cold I/R injury is protective, not causative, we cultured rat H9C2 cells, the most commonly used heart cell line for in vitro studies of I/R [19]. H9C2 cells were transfected with a clusterin expression adenovirus prior to exposure to 16 h cold hypoxia at 10°C followed by 24 h reperfusion at 37°C in vitro.…”

Section: Clusterin Protects Cardiomyocytes From Cell Apoptosis Inducementioning

confidence: 99%

Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression

Liu

Zhang

Hao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury. Methods: Heart grafts from wild-type C57BL/6 mice were preserved in UW solution (control) or UW solution containing recombinant human apolipoprotein-J (hr clusterin) for 24 h. The preserved hearts were implanted into recipient mice of the same strain as the donors for 72 h, and the heart grafts were then taken for histopathological and gene expression analyses. An in vitro ischemia reperfusion model using H9C2 cells or H9C2/clusterin cDNA cells was constructed. The expression of clusterin, p65, Bax, Bcl-xL, IL-1β, and TNF-α protein and mRNA in heart tissue and H9C2 cells was detected by western blot, reverse transcription-polymerase chain reaction (RT-PCR), and quantitative RT-PCR assays; IL-1β and TNF-α protein was detected by enzyme-linked immunosorbent assays; NF-kB activity was detected by an electrophoretic mobility shift assay; cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometric analyses. Results: Cold I/R caused severe morphologic myocardial injury to heart grafts from wild-type C57BL/6 mice, whereas grafts from hr clusterin preservation showed less damage, as demonstrated by decreased cell apoptosis/death, decreased neutrophil infiltration, and the preservation of the normal structure of the heart. Clusterin reduced the expression of p65, pre-inflammatory IL-1β, and TNF-α, and the pro-apoptotic gene Bax, while it enhanced

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Protein kinase C (PKC) mediated interaction between conexin43 (Cx43) and K+(ATP) channel subunit (Kir6.1) in cardiomyocyte mitochondria: Implications in cytoprotection against hypoxia induced cell apoptosis

Cited by 58 publications

References 29 publications

Altered signaling pathways linked to angiotensin II underpin the upregulation of renal Na+-ATPase in chronically undernourished rats

Altered signaling pathways linked to angiotensin II underpin the upregulation of renal Na+-ATPase in chronically undernourished rats

The Selective Degradation of Synaptic Connexin 43 Protein by Hypoxia-induced Autophagy Impairs Natural Killer Cell-mediated Tumor Cell Killing

Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression

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