title: Crosstalk between protective autophagy and NF-κB signal in high glucose-induced podocytes.
abstract: Despite a great deal of recent studies focused on the pivotal role of autophagy in maintaining podocyte energy homeostasis, the mechanisms of autophagy in regulating transcriptional factors under high glucose (HG) condition are not fully understood. Here, we evaluated the effect of HG on nuclear factor-kappa B (NF-κB) signaling and autophagic process. The results showed that HG promoted autophagy in podocytes. Bafilomycin A1 (Baf A1) further enhanced this effect, but 3-methyadenine (3-MA) inhibited it. The proautophagic effects of HG manifested in the form of enhanced podocyte expression of light chain 3 (LC3)-II. In these cells, blockade of NF-κB signal by ammonium pyrrolidinethiocarbamate constrained in effectively reducing LC3-II up-regulation and increasing podocyte apoptosis. Furthermore, the autophagy inhibitors, such as Baf A1 and 3-MA, significantly enhanced HG-induced NF-κB activation and increased apoptosis. Thus, we conclude that the accumulation of autophagosomes results from enhancement of the autophagic flux, but not the blockage of autophagosome-lysosome fusion by HG. We also prove that HG-induced apoptosis, autophagy, and NF-κB signal are in a close crosstalk through a yet undetermined mechanism in podocytes.
authors: College of Medicine, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
authors: Miaomiao
authors: M
authors: Wei
authors: Zhigui
authors: Z
authors: Li
authors: Zhuo
authors: Z
authors: Yang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018942:Macrolides; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; C025946:3-methyladenine; C040929:bafilomycin A1; D005947:Glucose; D000225:Adenine