Necroptosis, a novel form of caspase-independent cell death, contributes to renal epithelial cell damage in an ATP-depleted renal ischemia model.
Acute kidney injury (AKI) induced by renal ischemia is a common clinical problem associated with a high morbidity and mortality. The present study investigated whether necroptosis was present in an in vitro renal ischemia model and whether the addition of necrostatin-1 (Nec-1) has a protective effect. In addition, whether autophagy was inhibited following the use of Nec-1 was also examined. When apoptosis was inhibited by z-VAD‑fmk and energy was depleted with antimycin A for 1 h, the morphological abnormalities of human proximal tubular epithelial (HK-2) cells were markedly attenuated, and the cell viability was significantly improved following incubation with Nec-1. LC3-II/I ratios and LC3-II/GAPDH ratios demonstrated a statistically significant decrease in the Nec-1 + tumor necrosis factor (TNF)-α + z-VAD-fmk + antimycin A (1 h) group compared with the control group. In conclusion, the present study suggested that necroptosis was present in HK-2 cells subjected to TNF-α stimulation and energy depletion. Nec-1 inhibits a caspase‑independent necroptotic pathway involving autophagy and may have therapeutic potential to prevent and treat renal ischemic injury.
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Xinling
X
Liang
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Yuanhan
Y
Chen
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Li
L
Zhang
Department of Nephrology, Central Hospital of Hengyang, Hengyang, Hunan 421001, P.R. China.
Fen
F
Jiang
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Wenjian
W
Wang
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Zhiming
Z
Ye
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Shuangxin
S
Liu
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Chunping
C
Yu
Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Wei
W
Shi
D000255:Adenosine Triphosphate / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009336:Necrosis; D020011:Protective Agents / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D007093:Imidazoles; D007211:Indoles; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C507699:necrostatin-1; D000255:Adenosine Triphosphate