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ENOS deficiency causes podocyte injury with mitochondrial abnormality
- Source :
- Free Radical Biology and Medicine. 87:181-192
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- Male
medicine.medical_specialty
Mitochondrial DNA
Nitric Oxide Synthase Type III
Renal cortex
Kidney Glomerulus
Mitochondrion
Biology
Nitric Oxide
medicine.disease_cause
Biochemistry
Podocyte
Muscle hypertrophy
Mice
Adenosine Triphosphate
Enos
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Mice, Knockout
Podocytes
Glomerular Hypertrophy
biology.organism_classification
Mitochondria
Oxidative Stress
medicine.anatomical_structure
Endocrinology
Kidney Diseases
Oxidation-Reduction
Oxidative stress
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....d55861f0c0a0fc98e5c4dadc976b7d83