Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism

Ravindran, Jayaraj; Gupta, Nimesh; Agrawal, Mona; Bhaskar, A.S.B.; Rao, P. Venkata

doi:10.1007/s10495-010-0554-0

Cited by 117 publications

(82 citation statements)

References 56 publications

(61 reference statements)

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“…32 Mitochondrial dysfunction activates caspases and promotes apoptosis. 53 Here, we have shown that HEP-Flury and particularly GD-SH-01 activate apoptosis and provoke a decrease of the MMP simultaneously. Autophagy as well as apoptosis constitutes 2 intracellular processes through which superfluous, damaged or aged cells or organelles are eliminated and several reports have provided evidence for a connection between these 2 pathways.…”

Section: Discussionmentioning

confidence: 64%

Wild-type rabies virus induces autophagy in human and mouse neuroblastoma cell lines

Peng

Sheng-He

et al. 2016

Autophagy

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Different rabies virus (RABV) strains have their own biological characteristics, but little is known about their respective impact on autophagy. Therefore, we evaluated whether attenuated RABV HEP-Flury and wildtype RABV GD-SH-01 strains triggered autophagy. We found that GD-SH-01 infection significantly increased the number of autophagy-like vesicles, the accumulation of enhanced green fluorescent protein (EGFP)-LC3 fluorescence puncta and the conversion of LC3-I to LC3-II, while HEP-Flury was not able to induce this phenomenon. When evaluating autophagic flux, we found that GD-SH-01 infection triggers a complete autophagic response in the human neuroblastoma cell line (SK), while autophagosome fusion with lysosomes was inhibited in a mouse neuroblastoma cell line (NA). In these cells, GD-SH-01 led to apoptosis and mitochondrial dysfunction while triggering autophagy, and apoptosis could be decreased by enhancing autophagy. To further identify the virus constituent causing autophagy, 5 chimeric recombinant viruses carrying single genes of HEP-Flury instead of those of GD-SH-01 were rescued. While the HEP-Flury virus carrying the wild-type matrix protein (M) gene of RABV triggered LC3-I to LC3-II conversion in SK and NA cells, replacement of genes of nucleoprotein (N), phosphoprotein (P) and glycoprotein (G) produced only minor autophagy. But no one single structural protein of GD-SH-01 induced autophagy. Moreover, the AMPK signaling pathway was activated by GD-SH-01 in SK. Therefore, our data provide strong evidence that autophagy is induced by GD-SH-01 and can decrease apoptosis in vitro. Furthermore, the M gene of GD-SH-01 may cooperatively induce autophagy.

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Section: Discussionmentioning

confidence: 64%

Wild-type rabies virus induces autophagy in human and mouse neuroblastoma cell lines

Peng

Sheng-He

et al. 2016

Autophagy

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“…Mitochondria-generated ROS plays a potent role in the release of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and apoptosis [21,37]. When the formation of ROS is enhanced, it can still influence the viability of cells and impair mitochondrial function, such as respiration and oxidative phosphorylation, mitochondrial permeability transition (MPT) and MMP.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the well-defined role of mitochondria in energy metabolism, regulation of cell apoptosis has recently emerged as second major function of these organelles [17][18][19][20][21][22]. Mitochondrion has an important role in caspase-dependant and caspase-independent pathways of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells

et al. 2012

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Various mechanical stresses can induce apoptosis of nucleus pulposus (NP) cells and intervertebral disc (IVD) degeneration in vivo, but the underlying molecular mechanism by which the number of NP cells is decreased in degenerated IVD is still not elucidated. The purpose of this study was to investigate whether the mitochondrial pathway is involved in compression-induced apoptosis of rabbit NP cells. The compression apparatus was used to investigate the effect of the compression in this process at one magnitude (1.0 MPa) for 6, 12, 18, 24 and 36 h. Cell viability was measured by cell counting kit-8. Apoptosis rate was analyzed by flow cytometry and the morphologic changes in apoptosis cells were observed by the phase-contrast microscopy and Hoechst 33258 staining. The apoptosis-related gene and protein synthesis, such as Bax, Bcl-2 and Caspase-3, was analyzed by real-time polymerase chain reaction and Western-blot, respectively. Mitochondrial function was evaluated by analyzing the mitochondrial permeability transition pore (MPTP), as well as reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The results indicated that compression at the magnitude of all time points induced apoptosis of rabbit NP cells in a time-dependent manner, and the cell viability was reduced significantly. Furthermore, the compression at this level profoundly suppressed the functions of the mitochondria such as the opening of MPTP, the excessive production of ROS and the decreased MMP. Our findings suggest that the compression-induced IVD degeneration is mediated, at least in part, via the mitochondrial apoptotic pathway in NP cells.

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“…33 Additionally, p38 MAPK is pivotal in the apoptosis induced by chemotherapy drugs. [34][35][36] In recent studies, the activation of p38 MAPK has been suggested to be induced by Aurora B kinase inhibition. 37,38 However, the role of p38 MAPK in VX680-induced effects remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer

Jin

Zhang

et al. 2016

Cancer Biology & Therapy

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VX680 is a potent and selective inhibitor that targets the Aurora kinase family. The p38 mitogen-activated protein kinase (MAPK) regulates a large number of cellular pathways and plays an important role in the regulation of cell survival and apoptosis. This study aimed to evaluate the effect of VX680 on cervical cancer cells and investigate whether the effects on apoptosis are enhanced by the ablation of p38 MAPK activation. The results suggested that VX680 inhibited the proliferation of cervical cancer cells by causing G2/M phase arrest and endoreduplication and that the apoptotic effect was attenuated by the activation of p38 MAPK. However, the addition of BIRB796, which is an important p38 MAPK inhibitor, effectively eliminated the expression of p-p38 and hence significantly enhanced the cell death induced by VX680 in vitro. Further study demonstrated that BIRB796 cooperated with VX680 to suppress cervical cancer cell growth in a mouse xenograft model. Taken together, our results demonstrated that VX680 induced cell cycle arrest and endoreduplication in human cervical cancer cells. Combined treatment with VX680 and BIRB796 synergistically inhibited tumor growth both in vitro and in vivo. Dual blockade of Aurora kinases and p38 MAPK is therefore a promising strategy for cervical cancer treatment.

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Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism

Cited by 117 publications

References 56 publications

Wild-type rabies virus induces autophagy in human and mouse neuroblastoma cell lines

Wild-type rabies virus induces autophagy in human and mouse neuroblastoma cell lines

Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells

The p38 MAPK inhibitor BIRB796 enhances the antitumor effects of VX680 in cervical cancer

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