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      The Release of Cyclophilin A from Rapamycin-Stimulated Vascular Smooth Muscle Cells Mediated by Myosin II Activation: Involvement of Apoptosis but Not Autophagy


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          Introduction: The exocytosis of cyclophilin A (CyPA) by a vesicular pathway in response to reactive oxygen species has been determined. However, other sources of extracellular CyPA remain obscure. Objective: The aim of this study was to determine the role of autophagy in the secretion of CyPA. Methods and Results: Rapamycin induced the activation of autophagy and release of CyPA from primary cultured rat aortic smooth muscle cells (RASMCs). However, inhibition of autophagy by knockdown of Atg7 or chloroquine did not affect the rapamycin-induced release of CyPA. With the exception of myosin II activity, rho-associated coiled-coil kinase (ROCK), actin remodelling, and synaptic vesicles were not implicated in the release of rapamycin-induced CyPA. Finally, we confirmed that rapamycin-induced extracellular CyPA originated from apoptotic RASMCs. Furthermore, the decreased activation of myosin II by blebbistatin blocked the release of CyPA from apoptotic RASMCs induced by rapamycin. Conclusions: Rapamycin induced the release of CyPA from apoptotic RASMCs but did not affect exocytosis through autophagosomes. ROCK, actin remodelling, and synaptic vesicles were not involved in the apoptosis-related release of CyPA. Myosin II activation modulated the apoptosis of vascular smooth muscle cells and the release of CyPA from rapamycin-induced apoptotic cell death.

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          Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells.

          Human embryonic stem cells (hESCs), unlike mouse ones (mESCs), are vulnerable to apoptosis upon dissociation. Here, we show that the apoptosis, which is of a nonanoikis type, is caused by ROCK-dependent hyperactivation of actomyosin and efficiently suppressed by the myosin inhibitor Blebbistatin. The actomyosin hyperactivation is triggered by the loss of E-cadherin-dependent intercellular contact and also observed in dissociated mouse epiblast-derived pluripotent cells but not in mESCs. We reveal that Abr, a unique Rho-GEF family factor containing a functional Rac-GAP domain, is an indispensable upstream regulator of the apoptosis and ROCK/myosin hyperactivation. Rho activation coupled with Rac inhibition is induced in hESCs upon dissociation, but not in Abr-depleted hESCs or mESCs. Furthermore, artificial Rho or ROCK activation with Rac inhibition restores the vulnerability of Abr-depleted hESCs to dissociation-induced apoptosis. Thus, the Abr-dependent "Rho-high/Rac-low" state plays a decisive role in initiating the dissociation-induced actomyosin hyperactivation and apoptosis in hESCs. Copyright 2010 Elsevier Inc. All rights reserved.
            • Record: found
            • Abstract: not found
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            Cell biology. Unconventional secretion, unconventional solutions.

              • Record: found
              • Abstract: found
              • Article: not found

              Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo.

              Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemotherapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c in the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                September 2020
                11 June 2020
                : 57
                : 5
                : 254-260
                aDepartment of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, and Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China
                bDepartment of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, China
                cDepartment of Hematocyte Morphological Lab, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
                Author notes
                *Dr. Shuanglun Xie, Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China), xieshuanglun@sina.com
                506685 J Vasc Res 2020;57:254–260
                © 2020 S. Karger AG, Basel

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                Page count
                Figures: 3, Pages: 7
                Research Article


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