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Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells.

Publication ,  Journal Article
Souma, T; Abe, M; Moriguchi, T; Takai, J; Yanagisawa-Miyazawa, N; Shibata, E; Akiyama, Y; Toyohara, T; Suzuki, T; Tanemoto, M; Abe, T; Sato, H ...
Published in: J Am Soc Nephrol
April 2011

A highly acidic environment surrounds proximal tubular cells as a result of their reabsorption of HCO(3)(-). It is unclear whether this luminal acidity affects proteinuria-induced progression of tubular cell damage. Here, we investigated the contribution of luminal acidity to superoxide (O(2)(·-)) production induced by oleic acid-bound albumin (OA-Alb) in proximal tubular cells. Acidic media significantly enhanced OA-Alb-induced O(2)(·-) production in the HK-2 proximal tubular cell line. Simultaneous treatment with both OA-Alb and acidic media led to phosphorylation of the intracellular pH sensor Pyk2. Highly phosphorylated Pyk2 associated with activation of Rac1, an essential subcomponent of NAD(P)H oxidase. Furthermore, knockdown of Pyk2 with siRNA attenuated the O(2)(·-) production induced by cotreatment with OA-Alb and acid. To assess whether luminal alkalinization abrogates proteinuria-induced tubular damage, we studied a mouse model of protein-overload nephropathy. NaHCO(3) feeding selectively alkalinized the urine and dramatically attenuated the accumulation of O(2)(·-)-induced DNA damage and proximal tubular injury. Overall, these observations suggest that luminal acidity aggravates proteinuria-induced tubular damage and that modulation of this acidic environment may hold potential as a therapeutic target for proteinuric kidney disease.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

April 2011

Volume

22

Issue

4

Start / End Page

635 / 648

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Sodium Bicarbonate
  • Reactive Oxygen Species
  • Proteinuria
  • Oxygen
  • Oxidative Stress
  • Oleic Acid
  • NADPH Oxidases
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Souma, T., Abe, M., Moriguchi, T., Takai, J., Yanagisawa-Miyazawa, N., Shibata, E., … Ito, S. (2011). Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells. J Am Soc Nephrol, 22(4), 635–648. https://doi.org/10.1681/ASN.2009111130
Souma, Tomokazu, Michiaki Abe, Takashi Moriguchi, Jun Takai, Noriko Yanagisawa-Miyazawa, Eisuke Shibata, Yasutoshi Akiyama, et al. “Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells.J Am Soc Nephrol 22, no. 4 (April 2011): 635–48. https://doi.org/10.1681/ASN.2009111130.
Souma T, Abe M, Moriguchi T, Takai J, Yanagisawa-Miyazawa N, Shibata E, et al. Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells. J Am Soc Nephrol. 2011 Apr;22(4):635–48.
Souma, Tomokazu, et al. “Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells.J Am Soc Nephrol, vol. 22, no. 4, Apr. 2011, pp. 635–48. Pubmed, doi:10.1681/ASN.2009111130.
Souma T, Abe M, Moriguchi T, Takai J, Yanagisawa-Miyazawa N, Shibata E, Akiyama Y, Toyohara T, Suzuki T, Tanemoto M, Abe T, Sato H, Yamamoto M, Ito S. Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells. J Am Soc Nephrol. 2011 Apr;22(4):635–648.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

April 2011

Volume

22

Issue

4

Start / End Page

635 / 648

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Sodium Bicarbonate
  • Reactive Oxygen Species
  • Proteinuria
  • Oxygen
  • Oxidative Stress
  • Oleic Acid
  • NADPH Oxidases
  • Mice, Inbred C57BL
  • Mice