Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins

Zepeta-Flores, Nahum; Valverde, Mahara; López-Saavedra, Alejandro; Rojas, Emilio

doi:10.1590/1678-4685-gmb-2017-0158

Cited by 7 publications

(3 citation statements)

References 51 publications

(60 reference statements)

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“…Actin filaments regulate autophagy ( 21 ) and are severed by GSN in a calcium-dependent manner ( 23 , 26 , 32 , 33 ). Nonetheless, the role of the actin cytoskeleton in autophagy in PDECs in AP is incompletely understood.…”

Section: Discussionmentioning

confidence: 99%

Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

Yang

Liang

Xie

et al. 2023

Braz J Med Biol Res

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Gelsolin (GSN) can sever actin filaments associated with autophagy. This study investigated how GSN-regulated actin filaments control autophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP). AP was produced in a rat model and PDECs using caerulein (CAE). Rat pancreatic duct tissue and HPDE6-C7 cells were extracted at 6, 12, 24, and 48 h after CAE treatment. HPDE6-C7 cells in the presence of CAE were treated with cytochalasin B (CB) or silenced for GSN for 24 h. Pancreatic histopathology and serum amylase levels were analyzed. Cellular ultrastructure and autophagy in PDECs were observed by transmission electron microscopy after 24 h of CAE treatment. The expression of GSN and autophagy markers LC3, P62, and LAMP2 was evaluated in PDECs by immunohistochemistry and western blotting. Actin filaments were observed microscopically. Amylase levels were highest at 6 h of AP, and pancreatic tissue damage increased over time. Mitochondrial vacuolization and autophagy were observed in PDECs. CAE increased GSN expression in these cells over time, increased the LC3-II/LC3-I ratio and LAMP2 expression at 24 and 6 h of treatment, respectively, and decreased P62 expression at all time points. CB treatment for 24 h decreased the LC3-II/LC3-I ratio and LAMP2 expression, increased P62 levels, but had no impact on GSN expression in CAE-treated PDECs. CAE induced actin depolymerization, and CB potentiated this effect. GSN silencing increased the LC3-II/LC3-I ratio and LAMP2 expression and reduced actin depolymerization in CAE-treated PDECs. GSN may inhibit autophagosome biogenesis and autophagosome-lysosome fusion by increasing actin depolymerization in PDECs in AP.

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Section: Discussionmentioning

confidence: 99%

Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

Yang

Liang

Xie

et al. 2023

Braz J Med Biol Res

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“…For treatment experiments, control and DJ‐1 shRNA M17 cells ( n = 4) were treated with either regular media or buthionine sulfoximine (43 mM) for 8 h. Following treatment, cells were processed for DNA, RNA, and protein isolation (see below). Treatment concentrations used were the IC 50 determined by toxicity following 24 h treatment exposure using 0, 0.1, 1, 10, and 100 mM for buthionine sulfoximine (Zepeta‐Flores et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

DJ‐1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons

Mazza

Shuck

Lin

et al. 2022

Journal of Neurochemistry

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Human DJ-1 is a cytoprotective protein whose absence causes Parkinson's disease and is also associated with other diseases. DJ-1 has an established role as a redoxregulated protein that defends against oxidative stress and mitochondrial dysfunction. Multiple studies have suggested that DJ-1 is also a protein/nucleic acid deglycase that plays a key role in the repair of glycation damage caused by methylglyoxal (MG), a reactive α-keto aldehyde formed by central metabolism. Contradictory reports suggest that DJ-1 is a glyoxalase but not a deglycase and does not play a major role in glycation defense. Resolving this issue is important for understanding how DJ-1 protects cells against insults that can cause disease. We find that DJ-1 reduces levels of reversible adducts of MG with guanine and cysteine in vitro. The steady-state kinetics of DJ-1 acting on reversible hemithioacetal substrates are fitted adequately with a computational kinetic model that requires only a DJ-1 glyoxalase activity, supporting the conclusion that deglycation is an apparent rather than a true activity of DJ-1.Sensitive and quantitative isotope-dilution mass spectrometry shows that DJ-1 modestly reduces the levels of some irreversible guanine and lysine glycation products in primary and cultured neuronal cell lines and whole mouse brain, consistent with a small but measurable effect on total neuronal glycation burden. However, DJ-1 does not improve cultured cell viability in exogenous MG. In total, our results suggest that DJ-1 is not a deglycase and has only a minor role in protecting neurons against methylglyoxal toxicity.

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“…Following treatment, cells were processed for DNA, RNA, and protein isolation (see below). Treatment concentrations used were the IC 50 determined by toxicity following 24 hr treatment exposure using 0, 0.1, 1, 10 and 100 mM for buthionine sulfoximine (83).…”

Section: Methodsmentioning

confidence: 99%

DJ-1 glyoxalase activity makes a modest contribution to cellular defense against methylglyoxal damage in neurons

Mazza

Shuck

Lin

et al. 2022

Preprint

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Human DJ-1 is a cytoprotective protein whose absence causes Parkinson's disease and is also associated with other diseases. DJ-1 has an established role as a redox-regulated protein that defends against oxidative stress and mitochondrial dysfunction. Multiple studies have suggested that DJ-1 is also a protein/nucleic acid deglycase that plays a key role in the repair of glycation damage caused by methylglyoxal (MG), a reactive α-keto aldehyde formed by central metabolism. Contradictory reports suggest that DJ-1 is a glyoxalase but not a deglycase and does not play a major role in glycation defense. Resolving this issue is important for understanding how DJ-1 protects cells against insults that can cause disease. We find that DJ-1 reduces levels of reversible adducts of MG with guanine and cysteine in vitro. The steady-state kinetics of DJ-1 acting on reversible hemithioacetal substrates are fitted adequately with a computational kinetic model that requires only a DJ-1 glyoxalase activity, supporting the conclusion that deglycation is an apparent rather than a true activity of DJ-1. Sensitive and quantitative isotope-dilution mass spectrometry shows that DJ-1 modestly reduces the levels of some irreversible guanine and lysine glycation products in primary and cultured neuronal cell lines and whole mouse brain, consistent with a small but measurable effect on total neuronal glycation burden. However, DJ-1 does not improve cultured cell viability in exogenous MG. In total, our results suggest that DJ-1 is not a deglycase and has only a minor role in protecting neurons against methylglyoxal toxicity.

show abstract

Glutathione depletion triggers actin cytoskeleton changes via actin-binding proteins

Cited by 7 publications

References 51 publications

Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

DJ‐1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons

DJ-1 glyoxalase activity makes a modest contribution to cellular defense against methylglyoxal damage in neurons

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