title: The ambiguous role of the Na+-H+ exchanger isoform 1 (NHE1) in leptin-induced oxidative stress in human monocytes.
abstract: Leptin, a 16-kDa cytokine produced mainly by the adipose tissue, is known to increase energy expenditure while at the same time lowering food intake by acting directly on the hypothalamus. ObRb, the leptin receptor mostly involved in intracellular signaling, is expressed in a wide range of tissues, thus allowing leptin to affect a much broader diversity of biological processes. High concentrations of leptin are encountered in patients with hyperleptinemia, a condition which very often accompanies obesity and which is a direct result of leptin resistance. In the present study, moderate and high concentrations of leptin (16 and 160 ng/ml) were mostly utilized in order to investigate the role of this cytokine in oxidative stress levels in human monocytes. Leptin was found to increase oxidative species production as measured with 2',7'-dichlorodihydrofluorescein diacetate (general marker of oxidative species, but not O2-*) and dihydroethidium (marker of O2-*). Surprisingly, it also augmented superoxide dismutase activity. Inhibition of the Na+-H+ exchanger isoform 1 (NHE1) also inhibited leptin-induced superoxide anion production but at the same time amplified leptin-induced production of other oxidative species. Signaling proteins such as phosphoinositide 3 kinase and conventional isoforms of protein kinase C (alpha-, beta(i)-, beta(ii)-), as well as NADPH oxidase, also participated in leptin signaling. Finally, leptin was found to increase glutathionylation levels of NHE1-bound heat shock protein 70 kDa (Hsp70) but not Hsp70 binding to NHE1.
authors.affiliation: Laboratory of Animal Physiology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Diamantis
authors.initials: D
authors.lastname: Konstantinidis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Paletas
authors.forename: George
authors.initials: G
authors.lastname: Koliakos
authors.forename: Martha
authors.initials: M
authors.lastname: Kaloyianni
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism*; D004996:Ethidium / Q000031:analogs & derivatives / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: C110400:2',7'-dichlorodihydrofluorescein diacetate; D027682:Cation Transport Proteins; D005452:Fluoresceins; D018840:HSP70 Heat-Shock Proteins; D020738:Leptin; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; C067883:dihydroethidium; D013481:Superoxides; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D004996:Ethidium