Inhibition of protein kinase C μ by various inhibitors. Inhibition from protein kinase c isoenzymes

Gschwendt, Michael; Dieterich, Sabine; Rennecke, Joerg; Kittstein, Walter; Mueller, Hans-Joachim; Johannes, Franz‐Josef

doi:10.1016/0014-5793(96)00785-5

Cited by 604 publications

(502 citation statements)

References 20 publications

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“…per 10 5 cells after 96 h treatment. The proliferative effects of UDCA were also reduced by Gö6976 ( Figure 4B), an inhibitor of PKC-a and -b that does not affect PKC-d (Gschwendt et al, 1996), confirming that both PKC and p42/44 MAP kinase are involved in mediating the effects of UDCA. The p38 MAP kinase inhibitor SB202190 had no effect on the proliferative effects of UDCA ( Figure 4B).…”

Section: Effect Of Pkc Map Kinase and Caspase 3 Inhibitors On The Acmentioning

confidence: 53%

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

et al. 2003

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Butyrate, produced in the colon by fermentation of dietary fibre, induces apoptosis in colon adenoma and cancer cell lines, which may contribute to protection against colorectal cancer. However, butyrate is present in the colon along with other dietary factors, including unconjugated bile acids, which are tumour promoters. We have shown previously that the proapoptotic effects of butyrate on AA/C1 human adenoma cells were reduced in the presence of bile acids. To determine the cellular basis of this interaction, we examined the effects of butyrate and the secondary bile acid ursodeoxycholic acid (UDCA) on signalling pathways known to regulate apoptosis using AA/C1 cells. Butyrate activated PKC-d and p38 MAP (mitogen-activated protein) kinase, whereas UDCA activated PKC-a and p42/44 MAP kinase. Butyrate treatment also resulted in the caspase-3-mediated proteolysis of PKC-d. Butyrate-induced apoptosis was reduced by inhibitors of PKC-d (Rottlerin), p38 MAP kinase (SB202190) and caspase 3 (DEVD-fmk), whereas the proliferative/survival effects of UDCA were blocked by inhibitors of PKC-a (Gö 6976) and MEK 1 (PD98059). The effects of butyrate and bile acids are therefore mediated by the differential activation of signalling pathways that are known to regulate apoptosis.

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Section: Effect Of Pkc Map Kinase and Caspase 3 Inhibitors On The Acmentioning

confidence: 53%

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

et al. 2003

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“…The second, Gö 6983, inhibits both classical and novel PKC isoforms, but does not inhibit PKD, and can thus be used to differentiate between PKDand PKC-dependent processes. 20 Inhibition of PKD by treatment of cells with Gö 6976 blocked the DAPk-induced JNK phosphorylation Figure 4a). In contrast, inhibition of other PKC isoforms by Gö 6983 had no effect on the DAPk-induced JNK phosphorylation, suggesting that DAPk functions in a PKCindependent manner (Figure 4a).…”

Section: Resultsmentioning

confidence: 99%

DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Eisenberg‐Lerner

Kimchi

2007

Cell Death Differ

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The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.

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“…PKCδ levels were similar in NL and DS cells (Figure 3d). To evaluate whether Nrf2 phosphorylation in DS cells is dependent on PKCδ kinase activity (Niture et al, 2009), we used the PKCδ inhibitor Gö6983 and also Gö6976, an inhibitor that do not affect PKCδ but interfere PKCα and PKCβ isoforms instead (Gschwendt et al, 1996; Martiny‐Baron et al, 1993; Stempka et al, 1999). Treatment with Gö6983 prevented pNrf2 nuclear translocation in both basal conditions and after PQ treatment, while Gö6976 had no effect (Figure 3e).…”

Section: Resultsmentioning

confidence: 99%

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Zamponi

Coşkun

et al. 2018

Aging Cell

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SummaryMounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by a complex phenotype, including early senescence. DS cells display increased levels of reactive oxygen species (ROS) and mitochondrial structural and metabolic dysfunction, which are counterbalanced by sustained Nrf2‐mediated transcription of cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCδdependent activation of the Nrf2 pathway in DS and Dp16 (a mouse model of DS) cells is necessary to protect against chronic oxidative damage and to preserve cellular functionality. Mitochondria‐targeted catalase (mCAT) significantly reduced oxidative stress, restored mitochondrial structure and function, normalized replicative and wound healing capacity, and rendered the Nrf2‐mediated antioxidant response dispensable. These results highlight the critical role of Nrf2/ARE in the maintenance of DS cell homeostasis and validate mitochondrial‐specific interventions as a key aspect of antioxidant and antiaging therapies.

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Inhibition of protein kinase C μ by various inhibitors. Inhibition from protein kinase c isoenzymes

Cited by 604 publications

References 20 publications

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

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