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2017 ; 8
(10
): e3099
Nephropedia Template TP
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Trehalose protects against cadmium-induced cytotoxicity in primary rat proximal
tubular cells via inhibiting apoptosis and restoring autophagic flux
#MMPMID29022917
Wang XY
; Yang H
; Wang MG
; Yang DB
; Wang ZY
; Wang L
Cell Death Dis
2017[Oct]; 8
(10
): e3099
PMID29022917
show ga
Autophagy has an important renoprotective function and we recently found that
autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we
aimed to investigate the protective effect of trehalose (Tre), a novel autophagy
activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT)
cells. First, data showed that Tre treatment significantly decreased Cd-induced
apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic
pathway, evidenced by morphological analysis, flow cytometric and immunoblot
assays. Also, administration with Tre protected rPT cells against Cd-induced
lipid peroxidation. Inhibition of autophagic flux in Cd-exposed rPT cells was
markedly restored by Tre administration, demonstrated by immunoblot analysis of
autophagy marker proteins and GFP and RFP tandemly tagged LC3 method.
Resultantly, Cd-induced autophagosome accumulation was obviously alleviated by
Tre treatment. Meanwhile, blockage of autophagosome-lysosome fusion by Cd
exposure was noticeably restored by Tre, which promoted the autophagic
degradation in Cd-exposed rPT cells. Moreover, Tre treatment markedly recovered
Cd-induced lysosomal alkalinization and impairment of lysosomal degradation
capacity in rPT cells, demonstrating that Tre has the ability to restore
Cd-impaired lysosomal function. Collectively, these findings demonstrate that Tre
treatment alleviates Cd-induced cytotoxicity in rPT cells by inhibiting apoptosis
and restoring autophagic flux.