Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: Relation to mitochondrial permeability transition

Srivastava, Shireesh; Chan, Christina

doi:10.1080/10715760600943900

Cited by 66 publications

(65 citation statements)

References 68 publications

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“…The aging-associated oxidative stress in the liver (Nakata et al 1996) was associated with ceramide elevation in the cells and could be mimicked by the dietetic saturated fatty acid supplementation to the adult animals (Nagle et al 2009). Exposure of palmitic acid to liver cells led to the timedependent reactive oxygen species (ROS) production (Strivastava and Chan 2007), ceramide accumulation (Wei et al 2006), apoptotic hepatocyte death, and development of hepatic insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Babenko

Hassouneh

Kharchenko

et al. 2011

AGE

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Sphingolipid turnover has been shown to be activated at old age and in response to various stress stimuli including oxidative stress. Reduction of vitamin E content in the liver under the pro-oxidant action is associated with enhanced sphingolipid turnover and ceramide accumulation in hepatocytes. In the present paper, the correction of sphingolipid metabolism in the liver cells of old rats and in the palmitate-treated young hepatocytes using α-tocopherol has been investigated. 3-and 24-month-old rats, [ 14 C] palmitic acid, [methyl− 14 C-choline]sphingomyelin (SM), and [ 14 C]serine were used. α-Tocopherol administration to old rats or addition to the culture medium of old liver slices or hepatocytes prevented age-dependent increase of ceramide synthesis and lipid accumulation, and increased SM content in liver tissue and cells. α-Tocopherol treatment of old cells decreased the neutral and acid sphingomyelinase (SMase) activities in hepatocytes and serine palmitoyl transferase activity in the liver cell microsomes. Effect of α-or γ-tocopherol, but not of δ-tocopherol, on the newly synthesized ceramide content in old cells was correlated with the action of inhibitor of serine palmitoyl transferase (SPT) activity (myriocin) and SMase inhibitors (glutathione, imipramine). Addition of α-tocopherol as well as myriocin to the culture medium of young hepatocytes, treated by palmitate, abolished ceramide accumulation and synthesis. The data obtained demonstrate that α-tocopherol normalized elevated ceramide content in the old liver cells via inhibition of acid and neutral SMase activities and lipid synthesis de novo. α-Tocopherol, reducing ceramide synthesis, prevented palmitate-induced aging-like ceramide accumulation in young liver cells.

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Section: Introductionmentioning

confidence: 99%

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Babenko

Hassouneh

Kharchenko

et al. 2011

AGE

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“…Palmitate is the most prevalent saturated fatty acid in circulation, and its level is further elevated in patients with NASH (37). The lipotoxic effect has been observed in pancreatic b-cells (47,93), cardiomyocytes (77,101), and hepatic cell lines (50,72,84,128,140,154). Molina et al, recently described a role for mitochondrial dynamics in the progression of the lipotoxic effect, or lipidinduced apoptosis, of FFA incubation in pancreatic b-cells (91).…”

Section: Metabolic Insult and Mitochondrial Dynamicsmentioning

confidence: 99%

Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

116

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Significance: Mitochondria are the cellular energy-producing organelles and are at the crossroad of determining cell life and death. As such, the function of mitochondria has been intensely studied in metabolic disorders, including diabetes and associated maladies commonly grouped under all-inclusive pathological condition of metabolic syndrome. More recently, the altered metabolic profiles and function of mitochondria in these ailments have been correlated with their aberrant morphologies. This review describes an overview of mitochondrial fission and fusion machineries, and discusses implications of mitochondrial morphology and function in these metabolic maladies. Recent Advances: Mitochondria undergo frequent morphological changes, altering the mitochondrial network organization in response to environmental cues, termed mitochondrial dynamics. Mitochondrial fission and fusion mediate morphological plasticity of mitochondria and are controlled by membrane-remodeling mechanochemical enzymes and accessory proteins. Growing evidence suggests that mitochondrial dynamics play an important role in diabetes establishment and progression as well as associated ailments, including, but not limited to, metabolism-secretion coupling in the pancreas, nonalcoholic fatty liver disease progression, and diabetic cardiomyopathy. Critical Issues: While mitochondrial dynamics are intimately associated with mitochondrial bioenergetics, their cause-and-effect correlation remains undefined in metabolic diseases. Future Directions: The involvement of mitochondrial dynamics in metabolic diseases is in its relatively early stages. Elucidating the role of mitochondrial dynamics in pathological metabolic conditions will aid in defining the intricate form-function correlation of mitochondria in metabolic pathologies and should provide not only important clues to metabolic disease progression, but also new therapeutic targets. Antioxid. Redox Signal. 19,[415][416][417][418][419][420][421][422][423][424][425][426][427][428][429][430]

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“…Generation of oxidative stress is an important factor in lipotoxicity by virtue of its contribution to cellular stress signaling and interference with mitochondrial functions (Srivastava and Chan, 2007). In a recent report, palmitate was demonstrated to limit GSH synthesis by inhibition of cysteine transporter xCT and subsequently limited substrate supply (Srivastava and Chan, 2008).…”

Section: Roles For Saturated and Monounsaturated Fatty Acids In Nonalmentioning

confidence: 99%

“…Thus, in addition to increasing intracellular levels of ROS, saturated fatty acids may also negatively affect the intracellular redox state by limiting the GSH-mediated oxidative defense. In particular, the ER (Borradaile et al, 2006a,b;Karaskov et al, 2006;Wei et al, 2006), mitochondrion (Maestre et al, 2003;Boudina et al, 2007;Srivastava and Chan, 2007;Koshkin et al, 2008), and lysosomes (Feldstein et al, 2004 were suggested as putative sites for lipotoxic stress induced by saturated free fatty acids. Finally, fatty acids were shown to induce apoptosis, an endpoint of lipotoxicity that is termed lipoapoptosis (Unger and Orci, 2002).…”

Section: Roles For Saturated and Monounsaturated Fatty Acids In Nonalmentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Anderson

Borlak²

2008

Pharmacol Rev

341

255

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Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: Relation to mitochondrial permeability transition

Cited by 66 publications

References 68 publications

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

Mitochondrial Morphology in Metabolic Diseases

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

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