Format

Send to

Choose Destination
Free Radic Biol Med. 2015 Oct;87:181-92. doi: 10.1016/j.freeradbiomed.2015.06.028. Epub 2015 Jun 26.

ENOS deficiency causes podocyte injury with mitochondrial abnormality.

Author information

1
TMK Project, Medical Innovation Center, Kyoto University, Kyoto, Japan; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
2
TMK Project, Medical Innovation Center, Kyoto University, Kyoto, Japan; Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan.
3
TMK Project, Medical Innovation Center, Kyoto University, Kyoto, Japan.
4
TMK Project, Medical Innovation Center, Kyoto University, Kyoto, Japan; Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
5
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
6
TMK Project, Medical Innovation Center, Kyoto University, Kyoto, Japan. Electronic address: nakagawt@gmail.com.

Abstract

The contribution of endothelial nitric oxide synthase (eNOS) to podocyte integrity remains unclear. This study therefore examined podocytes and mitochondrial abnormalities in eNOS deficient mice. Absence of eNOS caused glomerular hypertrophy, along with occasional glomerular sclerosis and mesangiolysis. While many glomeruli did not have such advanced lesions, ultrastructural analysis showed cellular hypertrophy, vacuolization, lysosomal enlargement, and microvillus formation in podocytes of eNOS knockout (KO) mice. Increased oxidative stress was associated with mitochondrial abnormalities, including an increase in number, coupled with a reduction in size, of mitochondria in podocytes of eNOS-KO mice. While the levels of expression of several mitochondrial proteins were not altered, the d-17 mutation in mitochondrial DNA was significantly associated with the eNOS deficiency. Renal ATP level in the renal cortex and mitochondrial respiration in the primary podocytes were significantly lower in eNOS-KO mice, suggesting that renal mitochondria may be functionally impaired. Podocytes cultured with endothelial conditioned medium lacking NO consistently showed a greater degree of mitochondrial fragmentation and an increase in mitochondrial oxidative stress, with these mitochondrial alterations rescued by an NO donor. In conclusion, eNOS may be necessary to maintain podocyte integrity, especially mitochondrial function.

KEYWORDS:

Endothelial; Glomerular; NO; Nitric oxide; Oxidative stress; Podocyte

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center