The RhoGDI-α/JNK signaling pathway plays a significant role in mycophenolic acid-induced apoptosis in an insulin-secreting cell line

Park, Yun Jong; Ahn, Hyung Joon; Chang, Hye Kyung; Kim, Joon Ye; Huh, Kyu Ha; Kim, Myoung Soo; Kim, Yu Seun

doi:10.1016/j.cellsig.2008.11.009

Cited by 28 publications

(17 citation statements)

References 46 publications

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“…MPA and its metabolites effect most of the cellular functions by influencing biological pathways, like apoptosis [5], immune associated signaling [6] and general cell signaling pathways involving mitogen-activated protein kinases, extracellular-signal regulated kinases, c-Jun N-terminal kinases, p53 and Rho-associated protein kinase [5,7,8]. Collectively, MPA possesses anti-microbial, anti-inflammatory, anti-fibrotic, pro-apoptotic [2], anti-angiogenic, anti-cancerous [9] and anti-oxidant activities [10].…”

Section: Introductionmentioning

confidence: 99%

Differential proteome analysis of human embryonic kidney cell line (HEK-293) following mycophenolic acid treatment

Qasim

Rahman

Oellerich³

et al. 2011

Proteome Sci

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BackgroundMycophenolic acid (MPA) is widely used as a post transplantation medicine to prevent acute organ rejection. In the present study we used proteomics approach to identify proteome alterations in human embryonic kidney cells (HEK-293) after treatment with therapeutic dose of MPA. Following 72 hours MPA treatment, total protein lysates were prepared, resolved by two dimensional gel electrophoresis and differentially expressed proteins were identified by QTOF-MS/MS analysis. Expressional regulations of selected proteins were further validated by real time PCR and Western blotting.ResultsThe proliferation assay demonstrated that therapeutic MPA concentration causes a dose dependent inhibition of HEK-293 cell proliferation. A significant apoptosis was observed after MPA treatment, as revealed by caspase 3 activity. Proteome analysis showed a total of 12 protein spots exhibiting differential expression after incubation with MPA, of which 7 proteins (complement component 1 Q subcomponent-binding protein, electron transfer flavoprotein subunit beta, cytochrome b-c1 complex subunit, peroxiredoxin 1, thioredoxin domain-containing protein 12, myosin regulatory light chain 2, and profilin 1) showed significant increase in their expression. The expression of 5 proteins (protein SET, stathmin, 40S ribosomal protein S12, histone H2B type 1 A, and histone H2B type 1-C/E/F/G/I) were down-regulated. MPA mainly altered the proteins associated with the cytoskeleton (26%), chromatin structure/dynamics (17%) and energy production/conversion (17%). Both real time PCR and Western blotting confirmed the regulation of myosin regulatory light chain 2 and peroxiredoxin 1 by MPA treatment. Furthermore, HT-29 cells treated with MPA and total kidney cell lysate from MMF treated rats showed similar increased expression of myosin regulatory light chain 2.ConclusionThe emerging use of MPA in diverse pathophysiological conditions demands in-depth studies to understand molecular basis of its therapeutic response. The present study identifies the myosin regulatory light chain 2 and peroxiredoxin 1 along with 10 other proteins showing significant regulation by MPA. Further characterization of these proteins may help to understand the diverse cellular effects of MPA in addition to its immunosuppressive activity.

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Section: Introductionmentioning

confidence: 99%

Differential proteome analysis of human embryonic kidney cell line (HEK-293) following mycophenolic acid treatment

Qasim

Rahman

Oellerich³

et al. 2011

Proteome Sci

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“…Many investigations have suggested that the expression level of RhoGDI-␣ closely modulates the JNK activity, which is strongly related to the apoptotic cell death (Muñoz-Alonso et al, 2008;Park et al, 2009). In this study we found that Fr-6 could knockdown the RhoGDI-␣ gene expression in human A549 cells and JNK inhibitor SP600125 could abrogate Fr-6-mediated JNK activation and cell death.…”

Section: Discussionmentioning

confidence: 49%

“…Using proteomic profiling combined with siRNA, MacKeigan et al (2003) discovered that in Taxol/MEK inhibitor-treated lung cancer H157 cell the expression of RhoGDI-␣ is diminished and RhoGDI-␣ expression knockdown by siRNA enhances the apoptosis of control, taxol-and MEK inhibitor-treated H157 cells. Park et al (2009) also found that the decreased RhoGDI-␣ expression level can induce the apoptosis of insulin-secreting cells through the activation of JNK pathway.…”

Section: Discussionmentioning

confidence: 87%

“…Recently the investigation by Park et al (2009) observed that the inhibition of RhoGDI-␣ production invokes the apoptosis of insulinsecreting cells by the activation of c-Jun NH 2 -terminal kinase (JNK) pathway. Since RhoGDI-␣ was suppressed in Fr-6-exposed human A549 cells, in this investigation we also explore if the JNK pathway was triggered in Fr-6-incubated human A549 cells.…”

Section: The Impact Of Fr-6 On the Expressions Of Four Tumor-related mentioning

confidence: 99%

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Apoptotic effects of a high performance liquid chromatography (HPLC) fraction of Antrodia camphorata mycelia are mediated by down-regulation of the expressions of four tumor-related genes in human non-small cell lung carcinoma A549 cell

Chan

Chang

Chien

et al. 2010

Journal of Ethnopharmacology

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“…The signal transduction mechanism underlying this process has not been fully explored. Using a proteomics approach, Park et al [39] examined protein expression patterns in MPA-treated apoptotic RIN-5 cells and found a decrease in the expression of RhoGDI-alpha. Over-expression of RhoGDI-alpha increased cell viability and decreased activated JNK expression following exposure to MPA, whereas knockdown of RhoGDI-alpha enhanced MPA-induced cell death and increased the activation of JNK.…”

Section: Chemical Compound-induced Apoptosismentioning

confidence: 99%

Current advances in the application of proteomics in apoptosis research

Wang

Chen

2011

Sci. China Life Sci.

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Apoptosis, or programmed cell death, is a complex, genetically-determined process involved in the development and maintenance of homeostasis in multicellular organisms. Dysregulation of apoptosis has been implicated in a number of diseases, including cancer and autoimmune disease. Thus, the investigation of apoptotic regulation has evoked considerable interest. Many apoptotic proteins have been shown to be post-translationally modulated, such as by protein cleavage, translocation, protein-protein interaction, and various post-translational modifications, which fall precisely within the range of proteomic analysis. Recently, contemporary proteomic technologies have achieved significant advances and have accelerated research in functional and chemical proteomics, which have been applied to the field of apoptosis research and have the potential to be a driving force for the field. This review highlights some of the major achievements in the application of proteomics in apoptosis research and discusses new directions and challenges for the near future.

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The RhoGDI-α/JNK signaling pathway plays a significant role in mycophenolic acid-induced apoptosis in an insulin-secreting cell line

Cited by 28 publications

References 46 publications

Differential proteome analysis of human embryonic kidney cell line (HEK-293) following mycophenolic acid treatment

Differential proteome analysis of human embryonic kidney cell line (HEK-293) following mycophenolic acid treatment

Apoptotic effects of a high performance liquid chromatography (HPLC) fraction of Antrodia camphorata mycelia are mediated by down-regulation of the expressions of four tumor-related genes in human non-small cell lung carcinoma A549 cell

Current advances in the application of proteomics in apoptosis research

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