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Nutrients 2018, 10(6), 689; https://doi.org/10.3390/nu10060689

Taurine Supplementation Alleviates Puromycin Aminonucleoside Damage by Modulating Endoplasmic Reticulum Stress and Mitochondrial-Related Apoptosis in Rat Kidney

1
Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
2
Interdipartimental University Center of Research “Adaptation and Regeneration of Tissues and Organs (ARTO)”, University of Brescia, 25123 Brescia, Italy
3
Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna-IZSLER, 25124 Brescia, Italy
4
Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Received: 12 April 2018 / Revised: 24 May 2018 / Accepted: 25 May 2018 / Published: 29 May 2018
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Abstract

Taurine (TAU) is a sulfur-containing beta amino acid that is not involved in protein composition and anabolism, conditionally essential in mammals provided through diet. Growing evidence supports a protective role of TAU supply in osmoregulation, calcium flux, and reduction of inflammation and oxidant damage in renal diseases like diabetes. Endoplasmic reticulum (ER) stress, due to abnormal proteostasis, is a contributor to nephrotic syndrome and related renal damage. Here, we investigated the effect of dietary TAU (1.5% in drinking water for 15 days) in an established rat model that mimics human minimal change nephrosis, consisting of a single puromycin aminonucleoside (PAN) injection (intraperitoneally 15 mg/100 g body weight), with sacrifice after eight days. TAU limited proteinuria and podocytes foot processes effacement, and balanced slit diaphragm nephrin and glomerular claudin 1 expressions. In cortical proximal tubules, TAU improved lysosomal density, ER perimeter, restored proper ER-mitochondria tethering and mitochondrial cristae, and decreased inflammation. Remarkably, TAU downregulated glomerular ER stress markers (GRP78, GRP94), pro-apoptotic C/EBP homologous protein, activated caspase 3, tubular caspase1, and mitochondrial chaperone GRP75, but maintained anti-apoptotic HSP25. In conclusion, TAU, by targeting upstream ER stress separate from mitochondria dysfunctions at crucial renal sites, might be a promising dietary supplement in the treatment of the drug-resistant nephrotic syndrome. View Full-Text
Keywords: apoptosis; endoplasmic reticulum stress; kidney; puromycin aminonucleoside; taurine; ultrastructure apoptosis; endoplasmic reticulum stress; kidney; puromycin aminonucleoside; taurine; ultrastructure
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    Description: Figure S1- 4HNE and CD68/ED1 renal expression- (A-C) 4HNE, index of mitochondrial uncoupling, was intense in renal cortex of PAN group, but reduced in PAN + TAU group. (E-G) CD68/ED1, recognized marker of macrophages, decreased in the tubular interstitium in PAN + TAU mice Bar=20 μm. Quantification of the immunopositivity for 4HNE in Figure S1D and for CD68/ED1 in Figure S1H.
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Stacchiotti, A.; Favero, G.; Lavazza, A.; Monsalve, M.; Rodella, L.F.; Rezzani, R. Taurine Supplementation Alleviates Puromycin Aminonucleoside Damage by Modulating Endoplasmic Reticulum Stress and Mitochondrial-Related Apoptosis in Rat Kidney. Nutrients 2018, 10, 689.

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