Role of Ca2+ signaling in initiation of stretch-induced apoptosis in neonatal heart cells

Liao, Xu; Tang, Aohan; Chen, Quan; Jin, Heling; Wu, Congjun; Chen, Lan‐Ying; Wang, Shi Qiang

doi:10.1016/j.bbrc.2003.09.023

Cited by 41 publications

(39 citation statements)

References 27 publications

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“…It is intriguing how the mechanical signal is sensed by different types of cardiac cells. Our recent data suggest Ca 2+ is important for mediating the conversion of mechanical signals to biological signals in cardiomyocytes [42]. Further study of the distinct molecular signaling in cardiomyocytes and cardiac fibroblasts could be helpful for better understanding and treatment of heart remodeling and associated diseases.…”

Section: Discussionmentioning

confidence: 88%

Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts

et al. 2004

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Heart remodeling is associated with the loss of cardiomyocytes and increase of fibrous tissue owing to abnormal mechanical load in a number of heart disease conditions. In present study, a well-described in vitro sustained stretch model was employed to study mechanical stretch-induced responses in both neonatal cardiomyocytes and cardiac fibroblasts. Cardiomyocytes, but not cardiac fibroblasts, underwent mitochondria-dependent apoptosis as evidenced by cytochrome c (cyto c) and Smac/DIABLO release from mitochondria into cytosol accompanied by mitochondrial membrane potential (∆ψ m ) reduction, indicative of mitochondrial permeability transition pore (PTP) opening. Cyclosporin A, an inhibitor of PTP, inhibited stretch-induced cyto c release, ∆ψ m reduction and apoptosis, suggesting an important role of mitochondrial PTP in stretch-induced apoptosis. The stretch also resulted in increased expression of the pro-apoptotic Bcl-2 family proteins, including Bax and Bad, in cardiomyocytes, but not in fibroblasts. Bax was accumulated in mitochondria following stretch. Cell permeable Bid-BH3 peptide could induce and facilitate stretch-induced apoptosis and ∆ψ m reduction in cardiomyocytes. These results suggest that Bcl-2 family proteins play an important role in coupling stretch signaling to mitochondrial death machinery, probably by targeting to PTP. Interestingly, the levels of p53 were increased at 12 h after stretch although we observed that Bax upregulation and apoptosis occurred as early as 1 h. Adenovirus delivered dominant negative p53 blocked Bax upregulation in cardiomyocytes but showed partial effect on preventing stretch-induced apoptosis, suggesting that p53 was only partially involved in mediating stretch-induced apoptosis. Furthermore, we showed that p21 was upregulated and cyclin B1 was downregulated only in cardiac fibroblasts, which may be associated with G 2 /M accumulation in response to mechanical stretch.

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Section: Discussionmentioning

confidence: 88%

Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts

et al. 2004

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“…Recent reports suggest that proteins of the TRP superfamily form mechanosensitive cation channels (Corey et al, 2004;Maroto et al, 2005). The rise of intracellular calcium in cardiac myocytes and vascular smooth muscle cells may be mediated also via stretch-activated channels (Calaghan et al, 2003;Liao et al, 2003;Zou et al, 2002) besides release of intracellular calcium stores and influxes through L-type cation channel and sodium-calcium exchanger.…”

Section: Discussionmentioning

confidence: 99%

TRPC1 expression and distribution in rat hearts

Huang¹,

Wang²,

Liu³

et al. 2009

Eur J Histochem

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Transient receptor potential canonical (TRPC) proteins have been identified as a family of plasma membrane calcium-permeable channels. TRPC proteins can be activated by various stimuli and act as cellular sensors in mammals. Stretch-activated ion channels (SACs) have been proposed to underlie cardiac mechano-electric feedback (MEF), although the molecular entity of SAC remains unknown. There is evidence suggesting that transient receptor potential canonical 1 (TRPC1) is a stretch-activated ion channel. As a non-selective cation channel, TRPC1 may cause stretch-induced depolarization and arrhythmia and thus may contribute to the MEF of the heart. In this study, we examined the expression patterns of TRPC1 in detail at both the mRNA and protein levels in rat hearts. We isolated total RNA from the left and right atria, and the left and right ventricles, and detected TRPC1 mRNA in these tissues using reverse-transcriptase polymerase chain reaction (RT-PCR). To study the protein localization and targeting, we performed immunohistochemistry and immunofluorescence labeling with the antibody against TRPC1. TRPC1 was detected in the cardiomyocytes of the ventricle and atrium at both the mRNA and protein levels. The cell membrane and Ttubule showed strong fluorescence labeling in the ventricular myocytes. Purkinje cells, the endothelial cells and smooth muscle cells of the coronary arterioles also displayed TRPC1 labeling. No TRPC1 was detected in fibroblasts. In conclusion, TRPC1 is widely expressed in the rat heart, including in working cells, Purkinje cells and vascular cells, suggesting that it plays an important role in the heart. The specific distribution pattern offered a useful insight into its function in adult rat ventricular cells. Further investigations are needed to clarify the role of TRPC1 in regulating cardiac activity, including cardiac MEF.

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“…Mechanosensory pathways also affect cell shape and normal cell-to-cell communication (113,134,143) and produce local alterations in the actin cytoskeleton that affect ion channel gating and responsiveness to ␤-adrenergic receptor signaling (19,68,135,136). Finally, there is some evidence to suggest that mechanical overload of cardiomyocytes can directly or indirectly lead to the induction of apoptosis (55,66). …”

Section: Consequences Of Mechanotransduction In Cardiomyocytesmentioning

confidence: 99%

Costameres, focal adhesions, and cardiomyocyte mechanotransduction

Samarel¹

2005

American Journal of Physiology-Heart and Circulatory Physiology

249

201

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Samarel, Allen M. Costameres, focal adhesions, and cardiomyocyte mechanotransduction. Am J Physiol Heart Circ Physiol 289: H2291-H2301, 2005; doi: 10.1152/ajpheart.00749.2005.-Mechanotransduction refers to the cellular mechanisms by which load-bearing cells sense physical forces, transduce the forces into biochemical signals, and generate appropriate responses leading to alterations in cellular structure and function. This process affects the beat-to-beat regulation of cardiac performance but also affects the proliferation, differentiation, growth, and survival of the cellular components that comprise the human myocardium. This review focuses on the experimental evidence indicating that the costamere and its structurally related structure the focal adhesion complex are critical cytoskeletal elements involved in cardiomyocyte mechanotransduction. Biochemical signals originating from the extracellular matrix-integrin-costameric protein complex share many common features with those signals generated by growth factor receptors. The roles of key regulatory kinases and other muscle-specific proteins involved in mechanotransduction and growth factor signaling are discussed, and issues requiring further study in this field are outlined.focal adhesion kinase; proline-rich tyrosine kinase 2; integrin-linked kinase; protein kinase C; signal transduction; heart THE PROCESS OF MECHANOTRANSDUCTION refers to the cellular mechanisms by which load-bearing cells sense physical forces, transduce the forces into biochemical signals, and generate appropriate responses leading to alterations in cellular structure and function. Physical forces encountered by living cells include membrane stretch, gain and loss of adhesion, and compression due to an increase in pressure. The signal transduction pathways that are activated in response to mechanical forces include many unique components, as well as elements shared by other signaling pathways. Mechanotransduction in cardiomyocytes is particularly complex, in that individual muscle cells both respond to externally applied mechanical forces as well as generate internal loads that are transmitted to adjacent cells and their surrounding extracellular matrix (ECM). Mechanotransduction in both atrial and ventricular cardiomyocytes affects the beat-to-beat regulation of cardiac performance but also profoundly affects the proliferation, differentiation, growth, and survival of the cellular components that comprise the human myocardium. Understanding the cellular and molecular basis for mechanotransduction is therefore important to our overall understanding of cardiac structure and function in the normal and diseased heart.Observational studies conducted during the 1970s addressing the hypertrophic growth response of human myocardium to pathological changes in systolic and diastolic wall stress (42) fostered the development of experimental model systems with which to explore cardiomyocyte mechanotransduction in vivo and in vitro. These model systems now span the breadth of experimental cardiology...

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Role of Ca2+ signaling in initiation of stretch-induced apoptosis in neonatal heart cells

Cited by 41 publications

References 27 publications

Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts

Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts

TRPC1 expression and distribution in rat hearts

Costameres, focal adhesions, and cardiomyocyte mechanotransduction

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