scholarly journals Perfluorooctane sulfonate induces autophagy-associated apoptosis through oxidative stress and the activation of extracellular signal–regulated kinases in renal tubular cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245442
Author(s):  
Li-Li Wen ◽  
Yen-Ting Chen ◽  
Yuan-Chii Gladys Lee ◽  
Tsui-Ling Ko ◽  
Hsiu-Chu Chou ◽  
...  
Keyword(s):  
Perfluorooctane Sulfonate ◽  
Mitogen Activated Protein Kinase ◽  
Prolonged Treatment ◽  
Autophagic Flux ◽  
Protein Accumulation ◽  
Acridine Orange Staining ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Extracellular Signal ◽  
Renal Tubular

Perfluorooctane sulfonate (PFOS) is among the most abundant organic pollutants and is widely distributed in the environment, wildlife, and humans. Its toxic effects and biological hazards are associated with its long elimination half-life in humans. However, how it affects renal tubular cells (RTCs) remains unclear. In this study, PFOS was observed to mediate the increase in reactive oxygen species (ROS) generation, followed by the activation of the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway, which induced autophagy in RTCs. Although PFOS treatment induced autophagy after 6 h, prolonged treatment (24 h) reduced the autophagic flux by increasing lysosomal membrane permeability (LMP), leading to increased p62 protein accumulation and subsequent apoptosis. The increase in LMP was visualized through increased green fluorescence with acridine orange staining, and this was attenuated by 3-methyladenine, an autophagy inhibitor. N-acetyl cysteine and an inhibitor of the mitogen-activated protein kinase kinases (U0126) attenuated autophagy and apoptosis. Taken together, these results indicate that ROS activation and ROS-mediated phosphorylated ERK1/2 activation are essential to activate autophagy, resulting in the apoptosis of PFOS-treated RTCs. Our findings provide insight into the mechanism of PFOS-mediated renal toxicity.

ERK and p38 mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells

2004 ◽  
Vol 286 (1) ◽  
pp. F120-F126 ◽  
Author(s):  
Hisayo Fujita ◽  
Sayu Omori ◽  
Kenji Ishikura ◽  
Mariko Hida ◽  
Midori Awazu
Keyword(s):  
High Glucose ◽  
Transforming Growth Factor ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Leucine Incorporation ◽  
Renal Tubules ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Sb 203580

We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 And phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. Transforming growth factor (TGF)-β was expressed in all tubular segments of DM, coinciding with the localization of p38. In LLC-PK1 cells, phosphorylation of ERK and p38 increased after 24- to 72-h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [3H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-β protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF-β expression.

scholarly journals An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Maurizio Forte ◽  
Franca Bianchi ◽  
Maria Cotugno ◽  
Simona Marchitti ◽  
Rosita Stanzione ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
High Salt ◽  
Autophagic Flux ◽  
Protective Function ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Ros Accumulation ◽  
Renal Tubular

AbstractThe mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneously hypertensive rat. Overexpression of UCP2 counteracts the negative effects of high-salt feeding in both animal models. We tested in vitro the ability of UCP2 to stimulate autophagy and mitophagy as a mechanism mediating its protective effects upon high-salt exposure in endothelial and renal tubular cells. UCP2 silencing reduced autophagy and mitophagy, whereas the opposite was true upon UCP2 overexpression. High-salt exposure increased level of reactive oxygen species (ROS), UCP2, autophagy and autophagic flux in both endothelial and renal tubular cells. In contrast, high-salt was unable to induce autophagy and autophagic flux in UCP2-silenced cells, concomitantly with excessive ROS accumulation. The addition of an autophagy inducer, Tat-Beclin 1, rescued the viability of UCP2-silenced cells even when exposed to high-salt. In summary, UCP2 mediated the interaction between high-salt-induced oxidative stress and autophagy to preserve viability of both endothelial and renal tubular cells. In the presence of excessive ROS accumulation (achieved upon UCP2 silencing and high-salt exposure of silenced cells) autophagy was turned off. In this condition, an exogenous autophagy inducer rescued the cellular damage induced by excess ROS level. Our data confirm the protective role of UCP2 toward high-salt-induced vascular and renal injury, and they underscore the role of autophagy/mitophagy as a mechanism counteracting the high-salt-induced oxidative stress damage.

scholarly journals Human antigen R regulates hypoxia‐induced mitophagy in renal tubular cells through PARKIN/BNIP3L expressions

2021 ◽  
Author(s):  
Shao‐Hua Yu ◽  
Kalaiselvi Palanisamy ◽  
Kuo‐Ting Sun ◽  
Xin Li ◽  
Yao‐Ming Wang ◽  
...  
Keyword(s):  
Tubular Cells ◽  
Human Antigen R ◽  
Renal Tubular Cells ◽  
Renal Tubular

scholarly journals Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway

Renal Failure ◽  
2020 ◽  
Vol 42 (1) ◽  
pp. 381-390 ◽  
Author(s):  
Rong Tang ◽  
Xiangcheng Xiao ◽  
Yang Lu ◽  
Huihui Li ◽  
Qiaoling Zhou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tubular Cells ◽  
Interleukin 22 ◽  
Renal Tubular Cells ◽  
Notch1 Signaling ◽  
Renal Tubular ◽  
Notch1 Signaling Pathway ◽  
Tgf Β1

scholarly journals Hepatocyte Nuclear Factor-1β Controls Mitochondrial Respiration in Renal Tubular Cells

2017 ◽  
Vol 28 (11) ◽  
pp. 3205-3217 ◽  
Author(s):  
Audrey Casemayou ◽  
Audren Fournel ◽  
Alessia Bagattin ◽  
Joost Schanstra ◽  
Julie Belliere ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Dependency of Microdissected Nephron Segments upon Oxidative Phosphorylation and Exogenous Substrates: A Relationship between Tubular Anatomical Location in the Kidney and Metabolic Activity

1989 ◽  
Vol 77 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Shozo Torikai
Keyword(s):  
Collecting Duct ◽  
Anatomical Location ◽  
Thick Ascending Limb ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Nephron Segments ◽  
Henle's Loop ◽  
Renal Tubular ◽  
Substrate Deprivation ◽  
Exogenous Substrates

1. In order to examine the possibility of heterogeneity in the dependence of renal tubular cells upon oxidative phosphorylation and exogenous substrates, the effects of antimycin A and substrate deprivation on adenosine 5′-triphosphate (ATP) content were examined in isolated rat nephron segments in vitro at 37°C. 2. Antimycin A (5 μmol/l) caused varying decrements in cell ATP level within 5 min in the following order: proximal tubules > cortical thick ascending limb of Henle's loop (cTAL) > cortical collecting duct (cCD) in the cortex, and thin descending limb of Henle's loop (TDL) > medullary thick ascending limb of Henle's loop (mTAL) > outer medullary collecting duct (omCD) in the inner stripe of the outer medulla. In the thick ascending limb and the collecting duct, the segments located in the cortex were more sensitive than those in the medulla. 3. Substrate deprivation for 30 min markedly decreased the cell ATP content in cortical and medullary proximal tubules and also in medullary TDL, whereas it caused only a slight decrease in cTAL and mTAL with no change in cCD and omCD. 4. Media made hypertonic by the addition of 200 mmol/l NaCl under aerobic conditions, increased the requirement for exogenous substrates in TDL and mTAL, but not in omCD. This stimulation was seen to a lesser extent in media made hypertonic by the addition of mannitol instead of NaCl. 5. Taking into consideration a knowledge of rat kidney architecture and intrarenal gradient of oxygen partial pressure, it is likely that the observed dependency upon both oxygen and exogenous substrates in the renal tubular cells reflects adaptation of such cells to their anatomical location, and to the availability of those substances in situ. Furthermore, extracellular sodium concentration and osmolarity stimulate metabolic requirements to a different extent among the nephron segments.

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