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Ginseng total saponin modulates the changes of α-actinin-4 in podocytes induced by diabetic conditions.

Ha TS, Choi JY, Park HY, Nam JA, Seong SB - J Ginseng Res (2014)

Bottom Line: Diabetic conditions, including HG, AGE, and both together, decreased cellular α-actinin-4 protein levels at 24 h and 48 h.Such quantitative and qualitative changes of α-actinin-4 protein induced by diabetic conditions were mitigated by GTS.These findings imply that both HG and AGE have an influence on the distribution and amount of α-actinin-4 in podocytes that can be recovered by GTS.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea.

ABSTRACT

Background: The actin cytoskeleton in podocytes is essential for the maintenance of its normal structure and function. Its disruption is a feature of podocyte foot-process effacement and is associated with proteinuria. α-Actinin-4 in podocytes serves as a linker protein binding the actin filaments of the cytoskeleton.

Methods: To investigate the effect of ginseng total saponin (GTS) on the pathological changes of podocyte α-actinin-4 induced by diabetic conditions, we cultured mouse podocytes under normal glucose (5mM) or high glucose (HG, 30mM) conditions, with or without the addition of advanced glycosylation end products (AGE), and treated with GTS.

Results: In confocal imaging, α-actinin-4 colocalized with the ends of F-actin fibers in cytoplasm, but diabetic conditions disrupted F-actin fibers and concentrated α-actinin-4 molecules at the peripheral cytoplasm. GTS upregulated α-actinin protein in a time- and dose-dependent manner, and suppressed the receptor for AGE levels in western blotting. Diabetic conditions, including HG, AGE, and both together, decreased cellular α-actinin-4 protein levels at 24 h and 48 h. Such quantitative and qualitative changes of α-actinin-4 protein induced by diabetic conditions were mitigated by GTS.

Conclusion: These findings imply that both HG and AGE have an influence on the distribution and amount of α-actinin-4 in podocytes that can be recovered by GTS.

No MeSH data available.


Related in: MedlinePlus

Schematic view of cytoskeletal changes in the podocyte. Both high glucose and advanced glycosylation end products (AGE) induce the inner cytoplasmic relocalization and suppress the production of α-actinin-4 with the disruption of actin fibers, which were mitigated by ginseng total saponin (GTS).
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fig4: Schematic view of cytoskeletal changes in the podocyte. Both high glucose and advanced glycosylation end products (AGE) induce the inner cytoplasmic relocalization and suppress the production of α-actinin-4 with the disruption of actin fibers, which were mitigated by ginseng total saponin (GTS).

Mentions: The bands for α-actinin protein at 100 kDa were compared to those of β-tubulin. Density values for the α-actinin protein of representative immunoblots from each group revealed that HG (B30) suppressed the amount of α-actinin protein by 26.8% at 24 h and 24.1% at 48 h. These reductions were significant when compared with the control (B5). AGE (A5) alone or HG and AGE (A30) conditions also significantly suppressed the amount of α-actinin protein at 24 h and 48 h (p < 0.05) compared with B5 at 6 h after correcting for the β-tubulin levels (Figs. 3A and 3B). GTS (1 μg/mL) rescued the quantitative changes in the amount of α-actinin protein induced by diabetic conditions at 48 h (p < 0.05). Results on B5 and A30 podocytes were compared according to the exposure times given in Fig. 3C. These observations suggest that both HG and AGE induced cytoplasmic relocalization and concentration and suppressed the production of α-actinin-4 in an in vitro diabetic milieu, which could be mitigated by GTS (Fig. 4).


Ginseng total saponin modulates the changes of α-actinin-4 in podocytes induced by diabetic conditions.

Ha TS, Choi JY, Park HY, Nam JA, Seong SB - J Ginseng Res (2014)

Schematic view of cytoskeletal changes in the podocyte. Both high glucose and advanced glycosylation end products (AGE) induce the inner cytoplasmic relocalization and suppress the production of α-actinin-4 with the disruption of actin fibers, which were mitigated by ginseng total saponin (GTS).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4213837&req=5

fig4: Schematic view of cytoskeletal changes in the podocyte. Both high glucose and advanced glycosylation end products (AGE) induce the inner cytoplasmic relocalization and suppress the production of α-actinin-4 with the disruption of actin fibers, which were mitigated by ginseng total saponin (GTS).
Mentions: The bands for α-actinin protein at 100 kDa were compared to those of β-tubulin. Density values for the α-actinin protein of representative immunoblots from each group revealed that HG (B30) suppressed the amount of α-actinin protein by 26.8% at 24 h and 24.1% at 48 h. These reductions were significant when compared with the control (B5). AGE (A5) alone or HG and AGE (A30) conditions also significantly suppressed the amount of α-actinin protein at 24 h and 48 h (p < 0.05) compared with B5 at 6 h after correcting for the β-tubulin levels (Figs. 3A and 3B). GTS (1 μg/mL) rescued the quantitative changes in the amount of α-actinin protein induced by diabetic conditions at 48 h (p < 0.05). Results on B5 and A30 podocytes were compared according to the exposure times given in Fig. 3C. These observations suggest that both HG and AGE induced cytoplasmic relocalization and concentration and suppressed the production of α-actinin-4 in an in vitro diabetic milieu, which could be mitigated by GTS (Fig. 4).

Bottom Line: Diabetic conditions, including HG, AGE, and both together, decreased cellular α-actinin-4 protein levels at 24 h and 48 h.Such quantitative and qualitative changes of α-actinin-4 protein induced by diabetic conditions were mitigated by GTS.These findings imply that both HG and AGE have an influence on the distribution and amount of α-actinin-4 in podocytes that can be recovered by GTS.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea.

ABSTRACT

Background: The actin cytoskeleton in podocytes is essential for the maintenance of its normal structure and function. Its disruption is a feature of podocyte foot-process effacement and is associated with proteinuria. α-Actinin-4 in podocytes serves as a linker protein binding the actin filaments of the cytoskeleton.

Methods: To investigate the effect of ginseng total saponin (GTS) on the pathological changes of podocyte α-actinin-4 induced by diabetic conditions, we cultured mouse podocytes under normal glucose (5mM) or high glucose (HG, 30mM) conditions, with or without the addition of advanced glycosylation end products (AGE), and treated with GTS.

Results: In confocal imaging, α-actinin-4 colocalized with the ends of F-actin fibers in cytoplasm, but diabetic conditions disrupted F-actin fibers and concentrated α-actinin-4 molecules at the peripheral cytoplasm. GTS upregulated α-actinin protein in a time- and dose-dependent manner, and suppressed the receptor for AGE levels in western blotting. Diabetic conditions, including HG, AGE, and both together, decreased cellular α-actinin-4 protein levels at 24 h and 48 h. Such quantitative and qualitative changes of α-actinin-4 protein induced by diabetic conditions were mitigated by GTS.

Conclusion: These findings imply that both HG and AGE have an influence on the distribution and amount of α-actinin-4 in podocytes that can be recovered by GTS.

No MeSH data available.


Related in: MedlinePlus