Endoplasmic reticulum stress in the kidney

Abstract

Endoplasmic reticulum (ER) stress is involved in a wide range of pathological circumstances including neurodegenerative disorders, diabetes mellitus, ischemic injury, cancers, atherosclerosis, inflammation, infection, toxicity of chemicals and metals, and psychotic diseases. ER stress is also involved in some physiological events including development of particular cell types. A number of pathophysiological triggers cause accumulation of unfolded proteins in the ER, i.e., ER stress. In response to accumulation of unfolded/misfolded proteins, cells adapt themselves to the stress conditions via a coordinated adaptive program, the unfolded protein response (UPR). UPR is a double-edged sword. It induces both prosurvival and proapoptotic signaling. It also triggers both proinflammatory and anti-inflammatory signals. In this review, I summarize current knowledge on putative, pathophysiological roles of ER stress in the kidney.

TGP attenuates endoplasmic reticulum stress and regulates the expression of thioredoxin-interacting protein in the kidneys of diabetic rats

“…Fang et al reported that ERS appeared to play an important part in albuminuriaprovoked inflammasome activation and elimination of ERS via tauroursodeoxycholic acid (TUDCA), which might represent a novel avenue for attenuating kidney epithelial cell damage caused by albuminuria (34). The UPR is a homeostatic response that allows the cells to cope with stressful conditions associated with increased misfolded or unfolded protein loads; failure of this mechanism is referred to as the ERS response (9).The ERS response has been found to play a key role in a growing number of pathological conditions such as DN (10,34,35), and the ERS response is considered to be a cause of chronic inflammation (36). The current results verified the hypothesis that DN is related to ERS via dysregulated expression of GRP78, p-PERK, p-eIF2α, and CHOP.…”

“…GRP78 is a marker of ERS and has been implicated in the pathogenesis of diabetic complications (9). GRP78 was noted in the glomerulus and tubulointerstitium.…”

“…An ERS response maybe triggered by a stressful stimulus (e.g., hyperglycemia, oxidative stress, albuminuria, advanced glycation end products (AGEs), and activation of RAS (5)(6)(7)(8)), that exhausts or disrupts normal protein folding by the endoplasmic reticulum, thus causing accumulation of misfolded and/ or unfolded proteins. ERS may also activate the unfolded protein response (UPR) pathway that is initiated by glucose-regulated protein 78 (GRP78) and three endoplasmic reticulum transmembrane sensors -inositol requiring enzyme 1α (IRE1α), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6) (9). Therefore, the overexpression of IRE1α, PERK, and ATF6 contribute to a modified endoplasmic reticulum or the continued presence of unfolded proteins, resulting in insufficient protein folding.…”

Pomegranate (Punica granatum L.) reduces endoplasmic reticulum stress induced by renal ischemia/reperfusion injury in rat

“…Considering the key role of the ER in protein synthesis and proper folding, cellular stresses such as hypoxia, glucose depletion, and oxidative damage may lead to ER dysfunction and the accumulation of unfolded/misfolded proteins, which are categorized as ER stress (41). In response to these linked events, UPR as an adaptive or proapoptotic response will be activated (5,6). Herein, we have focused on transcription levels of the UPR markers GRP78 and XBP1 after induction of I/R in rat kidneys.…”

“…The endoplasmic reticulum (ER), as an important intracellular organelle responsible for protein synthesis, folding, trafficking, and modification, is susceptible to many stresses such as ischemia, oxidative stress, nutrient depletion, toxins, and hypoxia. These endogenous or exogenous disturbances can result in unfolded/misfolded protein accumulation and the subsequent activation of an unfolded protein response (UPR) (4)(5)(6)(7). Glucose-regulated protein (GRP) 78 (also known as BiP: immunoglobulin heavy-chain-binding protein) is a central modulator of the UPR that normally binds to and prevents aggregation of unfolded/misfolded proteins in the ER (6,8).…”