Cytosolic Dynamics of Annexin A6 Trigger Feedback Regulation of Hypertrophy via Atrial Natriuretic Peptide in Cardiomyocytes

Banerjee, Pradyot; Bandyopadhyay, Arun

doi:10.1074/jbc.m113.514810

Cited by 11 publications

(17 citation statements)

References 60 publications

(37 reference statements)

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“…Phenylephrine (PE from Sigma) dissolved in sterile water, bezafibrate and fenofibrate (from Sigma) dissolved in di-methyl sulfoxide (DMSO) were used for treatment in cell culture. Several earlier studies showed that 100 µM PE in 24 hours caused hypertrophy of cardiomyocytes in vitro [21,[25][26][27]. Therefore, in the present study, hypertrophy in H9c2 cardiomyocytes was induced by treatment with 100 µM PE for 24 hours.…”

Section: Methodsmentioning

confidence: 50%

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Targeting Peroxisome Proliferator Activated Receptor α (PPAR α) for the Prevention of Mitochondrial Impairment and Hypertrophy in Cardiomyocytes

Kar

Bandyopadhyay²

2018

Cell Physiol Biochem

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Background/Aims: Morphological and biochemical maladaptation of cardiomyocytes are associated with mitochondrial dysfunction and dysregulation in hypertrophic conditions. Peroxisome proliferator activated receptor α (PPARα), a drug target for dyslipidemia, is known to be downregulated in cardiomyocytes in response to hypertrophic stimuli. The current study was undertaken to investigate the role of PPARα signaling in mitochondrial remodeling and thereby dysregulation of cardiomyocytes due to hypertrophy in vitro. Methods: Rat cardiomyocytes H9c2 (2-1) and neonatal rat ventricular myocytes (NRVMs) were cultured and treated with α₁-adrenergic agonist phenylephrine (PE, 100 µM, 24 hours) in the presence or absence of 10 µM fenofibrate or bezafibrate. Cellular hypertrophy was observed by atomic force microscopy and immunofluorescence with F-actin antibody. mRNA levels of hypertrophic marker genes and other genes were examined by quantitative real time PCR. Structural as well as functional remodeling of the mitochondria were evaluated by immunofluorescence (F-actin and COX-I), live cell imaging microscopy (JC-I, mitotracker), mitochondrial complex V activity, MPTP activity and ATP assay. Oxidative stress was measured by using sensitive fluorescent indicator probes. Cellular and mitochondrial calcium were measured by using fluorescent indicator probes Rhod-2 AM and X-rhod-1 AM, respectively. Targetscan prediction analysis was performed to find out miRNAs as putative regulators of VDAC. Luciferase assay was conducted to confirm binding of miR28 with VDAC. Results: Co-treatment of H9c2(2-1) cells with PE and fenofibrate restricted increase in cell size and expression of marker genes such as atrial-natriuretic peptide (ANP), brain-natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) compared to those with PE alone. Fenofibrate prevented PE-induced down regulation of PPARα-target genes like CPT-I and MCAD. Mitochondrial trans-membrane potential (Δψ_m) and motility were reduced by PE which were significantly checked by fenofibrate. Increased ROS production and calcium level in PE-treated cells were ameliorated by fenofibrate. Mitochondrial activity and ATP generation were reduced by PE which was rescued by fenofibrate. Fenofibrate also prevented PE-induced down regulation of mitochondrial genes like VDAC-I and COX-IV. Expression of several miRNAs was altered in hypertrophic cardiomyocytes which were restored when co-treated with fenofibrate. miR28 was found to target 3’ untranslated region of VDAC-I. Conclusion: Overall, the results demonstrate that PPARα signaling is critically involved in mitochondrial dysfunction in hypertrophic cardiomyocytes in which miR28 plays a pivotal role.

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Section: Methodsmentioning

confidence: 50%

“…The spatial increase in cell size was analyzed by AFM of fixed cells as reported earlier with minor modifications [25]. Briefly, H9c2 cardiomyocytes were pretreated with or without 10 µM fenofibrate and incubated in the presence of 100 µM PE for 24 hours.…”

Section: Monitoring Cellular Hypertrophy By Atomic Force Microscopy (mentioning

confidence: 99%

Targeting Peroxisome Proliferator Activated Receptor α (PPAR α) for the Prevention of Mitochondrial Impairment and Hypertrophy in Cardiomyocytes

Kar

Bandyopadhyay²

2018

Cell Physiol Biochem

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“…Confocal imaging was performed on a TCS-SP8 platform (Leica Microsystems) equipped with ×63/1.4 NA oil, ×63/1.2 NA water, or ×40/1.2 NA oil objectives; 405/488/561/633 nm laser lines; and photomultiplier and hybrid (Leica HyD) detector systems. Highresolution images were acquired as described elsewhere (57,66). For faster time-lapse imaging, an 8K resonant scanner was used.…”

Section: Discussionmentioning

confidence: 99%

Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11

Tan

Banerjee

Guo

et al. 2016

Journal of Clinical Investigation

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“…Stained cells were visualized under a TCS SP8 confocal microscope (Leica Microsystems, Wetzlar, Germany) using a 63 × 1.4 numerical aperture oil objective. High-resolution images were acquired as described elsewhere54. Images were deconvolved, and colocalization was analyzed using Huygens Professional software (Scientific Volume Imaging B.V., Hilversum, The Netherlands).…”

Section: Methodsmentioning

confidence: 99%

FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch

Chen

Terajima

Banerjee

et al. 2017

Sci Rep

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Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular collagen cross-links (HLCCs). To test this hypothesis, we analyzed collagen cross-links in Fkbp10-null and –wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde–derived collagen cross-links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated collagen cross-linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities.

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Cytosolic Dynamics of Annexin A6 Trigger Feedback Regulation of Hypertrophy via Atrial Natriuretic Peptide in Cardiomyocytes

Cited by 11 publications

References 60 publications

Targeting Peroxisome Proliferator Activated Receptor α (PPAR α) for the Prevention of Mitochondrial Impairment and Hypertrophy in Cardiomyocytes

Targeting Peroxisome Proliferator Activated Receptor α (PPAR α) for the Prevention of Mitochondrial Impairment and Hypertrophy in Cardiomyocytes

Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11

FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven collagen cross-link switch

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