Abstract
ER stress has been implicated in the pathogenesis of both acute and chronic kidney diseases. However, the molecular regulation of ER stress in kidney cells and tissues remains poorly understood. In this study, we examined tunicamycin-induced ER stress in renal proximal tubular cells (RPTC). Tunicamycin induced the phosphorylation and activation of PERK and eIF2α within 2 h in RPTC, which was followed by the induction of GRP78 and CHOP. Consistently, tunicamycin also induced apoptosis in RPTC. Interestingly, mTOR was activated rapidly during tunicamycin treatment, as indicated by phosphorylation of both mTOR and p70S6K. Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment. Rapamycin also inhibited apoptosis during tunicamycin treatment and increased cell survival. Collectively, the results suggest that mTOR plays a regulatory role in ER stress, and inhibition of mTOR may have potential therapeutic effects in ER stress-related renal diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | F267-F274 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 308 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 2015 |
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Keywords
- Apoptosis
- Endoplasmic reticulum stress
- Mammmalian target of rapamycin
- Renal tubular cells
- Tunicamycin
ASJC Scopus subject areas
- Physiology
- Urology
Cite this
mTOR contributes to ER stress and associated apoptosis in renal tubular cells. / Dong, Guie; Liu, Yu; Zhang, Lei; Huang, Shuang; Ding, Han Fei; Dong, Zheng.
In: American Journal of Physiology - Renal Physiology, Vol. 308, No. 3, 01.01.2015, p. F267-F274.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - mTOR contributes to ER stress and associated apoptosis in renal tubular cells
AU - Dong, Guie
AU - Liu, Yu
AU - Zhang, Lei
AU - Huang, Shuang
AU - Ding, Han Fei
AU - Dong, Zheng
PY - 2015/1/1
Y1 - 2015/1/1
N2 - ER stress has been implicated in the pathogenesis of both acute and chronic kidney diseases. However, the molecular regulation of ER stress in kidney cells and tissues remains poorly understood. In this study, we examined tunicamycin-induced ER stress in renal proximal tubular cells (RPTC). Tunicamycin induced the phosphorylation and activation of PERK and eIF2α within 2 h in RPTC, which was followed by the induction of GRP78 and CHOP. Consistently, tunicamycin also induced apoptosis in RPTC. Interestingly, mTOR was activated rapidly during tunicamycin treatment, as indicated by phosphorylation of both mTOR and p70S6K. Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment. Rapamycin also inhibited apoptosis during tunicamycin treatment and increased cell survival. Collectively, the results suggest that mTOR plays a regulatory role in ER stress, and inhibition of mTOR may have potential therapeutic effects in ER stress-related renal diseases.
AB - ER stress has been implicated in the pathogenesis of both acute and chronic kidney diseases. However, the molecular regulation of ER stress in kidney cells and tissues remains poorly understood. In this study, we examined tunicamycin-induced ER stress in renal proximal tubular cells (RPTC). Tunicamycin induced the phosphorylation and activation of PERK and eIF2α within 2 h in RPTC, which was followed by the induction of GRP78 and CHOP. Consistently, tunicamycin also induced apoptosis in RPTC. Interestingly, mTOR was activated rapidly during tunicamycin treatment, as indicated by phosphorylation of both mTOR and p70S6K. Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment. Rapamycin also inhibited apoptosis during tunicamycin treatment and increased cell survival. Collectively, the results suggest that mTOR plays a regulatory role in ER stress, and inhibition of mTOR may have potential therapeutic effects in ER stress-related renal diseases.
KW - Apoptosis
KW - Endoplasmic reticulum stress
KW - Mammmalian target of rapamycin
KW - Renal tubular cells
KW - Tunicamycin
UR - http://www.scopus.com/inward/record.url?scp=84922227454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922227454&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00629.2014
DO - 10.1152/ajprenal.00629.2014
M3 - Article
C2 - 25428129
AN - SCOPUS:84922227454
VL - 308
SP - F267-F274
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 3
ER -