Hormetic and regulatory effects of lipid peroxidation mediators in pancreatic beta cells. (June 2016)

• Record Type: Journal Article
• Authors: Maulucci, Giuseppe; Daniel, Bareket; Cohen, Ofir; Avrahami, Yossef; Sasson, Shlomo
• Is Part Of: Molecular aspects of medicine. Volume 49(2016)
• Page Start: 49
• Page End: 77
• Publication Date: 2016-06
• Subjects: Beta cells -- Diabetes -- Eicosanoids -- Fatty aldehyde dehydrogenase -- Glutathione peroxidase -- Glutathione-S-transferase4-hydroxyalkenals -- 4-Hydroxynonenal -- Lipid peroxidation -- Phospholipase A; 12-HETE (PubChem CID: 5283155) -- 15-HETE (PubChem CID: 280724) -- 4-HNA (PubChem CID: 0442150) -- 12-HpETE (PubChem CID: 5283175) -- 15-HpETE (PubChem CID: 6437084) -- 13-HpODE (PubChem CID: 5280720) -- 13-HODE (PubChem CID: 5282947) -- 4-Hydroxy-2E, 6Z-dodecadienal (PubChem CID: 71340423) -- 4-Hydroxyl-2E-hexenal (PubChem CID: 5283314) -- 4-Hydroxy-2E-nonenal (PubChem CID: 5283344) -- PGD2 (PubChem CID: 448457) -- PGE2 (PubChem CID: 5280360) -- PGF2α (PubChem CID: 5280363) -- PGH2 (PubChem CID: 445049) -- PGI2 (PubChem CID: 6436393); 4-HDDE 4-hydroxy-2E, 6Z-dodecadienal -- 4-HHE 4-hydroxyl-2E-hexenal -- 4-HNA 4-hydroxynon-2-enoic acid -- 4-HNE 4-hydroxy-2E-nonenal -- AGE advanced glycation end products -- ADH alcohol dehydrogenase -- AR aldose reductase -- ARE antioxidant response element -- CaMKII Ca2+/calmodulin-dependent protein kinase II -- COX cyclooxygenase -- DAG diacylglycerol -- EET epoxyeicosatrienpic acid -- EGF epidermal growth factor -- EGRFR epidermal growth factor receptors -- ER endoplasmic reticulum -- ERK extracellular signal-regulated kinases -- FALDH fatty aldehyde dehydrogenase -- FDGFR platelet-derived growth factor receptor -- FFA1 free fatty acid receptor 1 -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- GLP-1 glucagon-like peptide-1 -- GP generalized polarization index -- GPx glutathione peroxidase -- GSH glutathione -- GSIS glucose-stimulated insulin secretion -- GST glutathione-S-transferase -- HETE hydroxyeicosatetraenoic acid -- HpETE hydroperoxyeicosatetraenoic acid -- HIF hypoxia-inducible factor -- HpODE hydroperoxyoctadecadienoic acid -- IKK IκB kinase -- IRS insulin receptor substrate -- JUNK c-Jun N-terminal kinase -- Keap1 Kelch-like ECH-associated protein -- Lck lymphocyte-specific protein tyrosine kinase -- LT leukotriene -- LO lipoxygenase -- MAPK mitogen-activated protein kinase -- MAPKK mitogen-activated protein kinase kinase -- mTOR mammalian target of rapamycin -- MUFA monounsaturated fatty acids -- Nrf2 nuclear factor (erythroid-derived 2)-like 2 -- NOS NO synthase -- NOX NADPH oxidase -- NQO1 NAD(P)H:quinone oxidoreductase -- PARP poly(ADP-ribose)-polymerase -- PKB/Akt protein kinase B -- PKC protein kinase C -- PDGFR platelet-derived growth factor receptors -- PIP3 phosphatidylinositol (3, 4, 5)-trisphosphate -- PI3K phosphatidylinositol-3-kinase -- PLA2 phospholipase A2 -- PPARδ peroxisome proliferator-activated receptor δ -- PTEN phosphatase and tensin homolog -- PTP protein tyrosine phosphatases -- PUFA polyunsaturated fatty acids -- ROS reactive oxygen species -- SOD superoxide dismutase -- S6K1 p70 ribosomal protein S6 kinase -- sEH soluble epoxide hydrolase -- SFA saturated fatty acids -- SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor -- T2DM type 2 diabetes mellitus -- UCP uncoupling protein -- Xpo1 export protein exportin1; Pathology, Molecular -- Periodicals; Medicine -- Periodicals; Biochemistry -- Periodicals; Medicine -- Periodicals; Molecular Biology -- Periodicals; Pathologie moléculaire -- Périodiques; Médecine -- Périodiques; Electronic journals; 612.015
• DOI: 10.1016/j.mam.2016.03.001
• Languages: English
• ISSNs: 0098-2997

Abstract

Abstract: Nutrient sensing mechanisms of carbohydrates, amino acids and lipids operate distinct pathways that are essential for the adaptation to varying metabolic conditions. The role of nutrient-induced biosynthesis of hormones is paramount for attaining metabolic homeostasis in the organism. Nutrient overload attenuate key metabolic cellular functions and interfere with hormonal-regulated inter- and intra-organ communication, which may ultimately lead to metabolic derangements. Hyperglycemia and high levels of saturated free fatty acids induce excessive production of oxygen free radicals in tissues and cells. This phenomenon, which is accentuated in both type-1 and type-2 diabetic patients, has been associated with the development of impaired glucose tolerance and the etiology of peripheral complications. However, low levels of the same free radicals also induce hormetic responses that protect cells against deleterious effects of the same radicals. Of interest is the role of hydroxyl radicals in initiating peroxidation of polyunsaturated fatty acids (PUFA) and generation of α, β-unsaturated reactive 4-hydroxyalkenals that avidly form covalent adducts with nucleophilic moieties in proteins, phospholipids and nucleic acids. Numerous studies have linked the lipid peroxidation product 4-hydroxy-2 E -nonenal (4-HNE) to different pathological and cytotoxic processes. Similarly, two other members of the family, 4-hydroxyl- 2E -hexenal (4-HHE) and 4-hydroxy-2E, 6Z-dodecadienal (4-HDDE), have also been identified as potential cytotoxic agents. It has been suggested that 4-HNE-induced modifications in macromolecules in cells may alter their cellular functions and modify signaling properties. Yet, it has also been acknowledged that these bioactive aldehydes also function as signaling molecules that directly modify cell functions in a hormetic fashion to enable cells adapt to various stressful stimuli. Recent studies have shown that 4-HNE and 4-HDDE, which activate peroxisome proliferator-activated receptor δ (PPARδ) in vascular endothelial cells and insulin secreting beta cells, promote such adaptive responses to ameliorate detrimental effects of high glucose and diabetes-like conditions. In addition, due to the electrophilic nature of these reactive aldehydes they form covalent adducts with electronegative moieties in proteins, phosphatidylethanolamine and nucleotides. Normally these non-enzymatic modifications are maintained below the cytotoxic range due to efficient cellular neutralization processes of 4-hydroxyalkenals. The major neutralizing enzymes include fatty aldehyde dehydrogenase (FALDH), aldose reductase (AR) and alcohol dehydrogenase (ADH), which transform the aldehyde to the corresponding carboxylic acid or alcohols, respectively, or by biding to the thiol group in glutathione (GSH) by the action of glutathione-S-transferase (GST). This review describes the hormetic and cytotoxic roles of oxygen free radicals and 4-hydroxyalkenals in beta cells exposed to nutritional challenges and the cellular mechanisms they employ to maintain their level at functional range below the cytotoxic threshold.