Albumin prevents reactive oxygen species-induced mitochondrial damage, autophagy, and apoptosis during serum starvation

The development of nonhormonal treatment of pemphigus vulgaris (PV) has been hampered by a lack of clear understanding of the mechanisms leading to keratinocyte (KC) detachment and death in pemphigus. In this study, we sought to identify changes in the vital mitochondrial functions in KCs treated with the sera from PV patients and healthy donors. PV sera significantly increased proton leakage from KCs, suggesting that PV IgGs increase production of reactive oxygen species. Indeed, measurement of intracellular reactive oxygen species production showed a drastic increase of cell staining in response to treatment by PV sera, which was confirmed by FACS analysis. Exposure of KCs to PV sera also caused dramatic changes in the mitochondrial membrane potential detected with the JC-1 dye. These changes can trigger the mitochondria-mediated intrinsic apoptosis. Although sera from different PV patients elicited unique patterns of mitochondrial damage, the mitochondria-protecting drugs nicotinamide (also called niacinamide), minocycline, and cyclosporine A exhibited a uniform protective effect. Their therapeutic activity was validated in the passive transfer model of PV in neonatal BALB/c mice. The highest efficacy of mitochondrial protection of the combination of these drugs found in mitochondrial assay was consistent with the ability of the same drug combination to abolish acantholysis in mouse skin. These findings provide a theoretical background for clinical reports of the efficacy of mitochondria-protecting drugs in PV patients. Pharmacological protection of mitochondria and/or compensation of an altered mitochondrial function may therefore become a novel approach to development of personalized nonhormonal therapies of patients with this potentially lethal autoimmune blistering disease.

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IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis

Acta Neuropathologica ◽

10.1007/s00401-017-1731-9 ◽

2017 ◽

Vol 134 (4) ◽

pp. 655-666 ◽

Cited By ~ 22

Author(s):

Alain Meyer ◽

Gilles Laverny ◽

Yves Allenbach ◽

Elise Grelet ◽

Vanessa Ueberschlag ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Mitochondrial Damage ◽

Oxygen Species ◽

Muscle Impairment

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Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1α and airway responsiveness to ACh

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00459.2006 ◽

2007 ◽

Vol 293 (4) ◽

pp. L913-L922 ◽

Cited By ~ 10

Author(s):

Georgia Chachami ◽

Apostolia Hatziefthimiou ◽

Panagiotis Liakos ◽

Maria G. Ioannou ◽

Georgios K. Koukoulis ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Smooth Muscle ◽

Airway Smooth Muscle ◽

Hypoxia Inducible Factor ◽

Reactive Oxygen ◽

Serum Starvation ◽

Airway Smooth Muscle Cells ◽

Oxygen Species ◽

Phosphatidylinositol 3 Kinase ◽

Phosphatidylinositol 3

Airway smooth muscle (ASM) cells are characterized by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, readdition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia-inducible factor (HIF)-1α. In addition, FBS stimulated the induction of HIF-1α by the hypoxia mimetic cobalt. Treatment with actinomycin D, cycloheximide, the phosphatidylinositol 3-kinase inhibitors LY-294002 and wortmannin or the reactive oxygen species scavenger diphenyleneiodonium inhibited the FBS-dependent induction of HIF-1α. These data indicate that, in differentiated ASM cells, FBS upregulates HIF-1α by a transcription-, translation-, phosphatidylinositol 3-kinase-, and reactive oxygen species-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1α in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh, suggesting that HIF-1α might be implicated in airway hypercontractility.

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Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1α Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species

Antioxidants ◽

10.3390/antiox9090820 ◽

2020 ◽

Vol 9 (9) ◽

pp. 820 ◽

Cited By ~ 1

Author(s):

Donghyun Kim ◽

Kyeong-A Kim ◽

Jeong-Hyeon Kim ◽

Eun-Hye Kim ◽

Ok-Nam Bae

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Endothelial Cells ◽

Tight Junction ◽

Reactive Oxygen ◽

Mitochondrial Damage ◽

Oxygen Species ◽

Brain Endothelial Cells ◽

Tight Junction Proteins ◽

Junction Proteins

Methylglyoxal (MG) is a dicarbonyl compound, the level of which is increased in the blood of diabetes patients. MG is reported to be involved in the development of cerebrovascular complications in diabetes, but the exact mechanisms need to be elucidated. Here, we investigated the possible roles of oxidative stress and mitophagy in MG-induced functional damage in brain endothelial cells (ECs). Treatment of MG significantly altered metabolic stress as observed by the oxygen-consumption rate and barrier-integrity as found in impaired trans-endothelial electrical resistance in brain ECs. The accumulation of MG adducts and the disturbance of the glyoxalase system, which are major detoxification enzymes of MG, occurred concurrently. Reactive oxygen species (ROS)-triggered oxidative damage was observed with increased mitochondrial ROS production and the suppressed Akt/hypoxia-inducible factor 1 alpha (HIF-1α) pathway. Along with the disturbance of mitochondrial bioenergetic function, parkin-1-mediated mitophagy was increased by MG. Treatment of N-acetyl cysteine significantly reversed mitochondrial damage and mitophagy. Notably, MG induced dysregulation of tight junction proteins including occludin, claudin-5, and zonula occluden-1 in brain ECs. Here, we propose that diabetic metabolite MG-associated oxidative stress may contribute to mitochondrial damage and autophagy in brain ECs, resulting in the dysregulation of tight junction proteins and the impairment of permeability.

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