Proteomic Analysis in Cyclosporin A-Induced Overgrowth of Human Gingival Fibroblasts

Jung, Ji Yeon; Kang, Gi Chang; Jeong, Yeon Jin; Kim, Sun Hun; Kwak, Yong-Geun; Kim, Won Jae

doi:10.1248/bpb.32.1480

Cited by 16 publications

(25 citation statements)

References 24 publications

(20 reference statements)

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“…Oxidative stress contributes to the pathophysiology of diverse clinical conditions, including ischemia-reperfusion mediated post transplantation graft injuries [28]. Prdx1 expression was also reported to be up-regulated in human gingival fibroblasts by cyclosporine A (another commonly used immunosuppressive drug) treatment [29]. MPA has previously been reported to diminish oxidative injuries and induce anti-oxidant effects by preventing the production of reactive oxygen species [10].…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…On the other hand, substances such as the immunosuppressive drug cyclosporine A (CsA), with an overgrowth effects on HGF in vitro , reduce the ROS production 14. CsA has no effects on cell division whereas inhibits apoptosis, upregulating the antiapoptotic protein Bcl‐2 and downregulating the proapoptotic protein Bax 15…”

Section: Introductionmentioning

confidence: 99%

Human gingival fibroblasts stress response to HEMA: A role for protein kinase C α

Cataldi

Zara

Rapino

et al. 2012

J Biomedical Materials Res

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2-Hydroxyethil methacrylate (HEMA), component of dentin-bonding systems, by diffusing into oral cavity induces a cytotoxic response. HEMA determines reactive oxygen species (ROS) production activating specific signaling pathways, including protein kinases C (PKC). In addition, since a regulation is exerted by various PKCs on nitric oxide synthase (NOS) activation, our aim was to investigate the role of PKCs and the possible interplay with ROS and NO signaling system in human gingival fibroblasts (HGF) response to HEMA. Cultured HGFs were exposed to 3 mM (a subtoxic concentration) HEMA for 0, 24, or 96 h. Each experimental point were processed for flow cytometry, fluorescence microscopy, western blotting, and "in vitro" NOS specific activity analyses. Three millimolar HEMA reduces HGF proliferation less than 50% and increases apoptosis percentage up to 18%. Both ROS production and PKC α expression and activation are also increased 96 h after HEMA exposure. The increased specific activity of iNOS, inflammatory enzyme, accompanied by Bax high expression in HGF response to 96 h HEMA, document the occurrence of an inflammatory and apoptotic response to such agent. Interestingly, a reduced percentage of apoptotic cells and a reduced ROS production are evidenced in the presence of bisindolylmaleide VIII, a PKC α pharmacologic inhibitor. All in all, these results suggest that PKC α can mediate the inflammatory response disclosed by gingival fibroblasts to HEMA released monomers.

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“…Data from references Shakib et al [58] and Li et al [33] were not included as they do not fulfill the table criteria. Cell lines used: Puigmule et al [26,70]: mouse renal proximal tubule cells (PKSV-PCT); Kang et al [26]: rat kidney interstitial fibroblasts -(NRK-49F); Hwang et al [34]: primary mouse mesangial cells; Malmstrom et al [25]: human fetal lung (HFL-1); Jung et al [71]: human gingival fibroblasts (HGF); Schordan et al [42]: mouse podocytes; So et al [41] and Chen et al [28]: human proximal tubule (HK-2); Boraldi et al [57]: human dermal fibroblasts. (continued on next page) (continued on next page) Rao and colleagues [32] examined changes in membrane and cytosolic subproteomes of human mesangial cells under high-glucose conditions, using 2-DE coupled with DeCyder analysis.…”

Section: High Glucosementioning

confidence: 99%

“…The second study was performed by Jung et al [71], who analyzed gingival fibroblasts (HGF) treated with CsA at 10 μM up to 48 h. Proteins profiled by 2-DE were identified by MALDI-TOF and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF MS). Seventeen significantly overexpressed proteins and three downregulated proteins were identified.…”

Section: Cyclosporine Amentioning

confidence: 99%

Renal fibrosis and proteomics: Current knowledge and still key open questions for proteomic investigation

Prunotto

Bruschi

Gabbiani

et al. 2011

Journal of Proteomics

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Proteomic Analysis in Cyclosporin A-Induced Overgrowth of Human Gingival Fibroblasts

Cited by 16 publications

References 24 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

Human gingival fibroblasts stress response to HEMA: A role for protein kinase C α

Renal fibrosis and proteomics: Current knowledge and still key open questions for proteomic investigation

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