title: [Regulatory mechanisms of intracellular distribution of Na+-dependent glucose transporter and the role in recovery from cellular injury].
abstract: Exposure of cells or organs to sublethal stress induces the expression of some heat-shock proteins (Hsp), including Hsp70. In porcine renal LLC-PK(1) cells, heat stress (HS) elevates Hsp70 expression and Na(+)-dependent glucose transport. We examined whether Na(+)-dependent glucose transporter (SGLT1) interacts with Hsp70 to elevate SGLT1 activity and whether SGLT1 activation is involved in the recovery from HS injury. HS (42 degrees C for 3 h) elevated SGLT1 activity and expression of SGLT1 in the apical membrane fraction. HS increased the maximal transport rate (V(max)), but did not affect the apparent affinity constant (K(m)) for glucose. The HS-induced SGLT1 activation was inhibited by anti-transforming growth factor (TGF)-beta1 antibody. Furthermore, transfection of anti-Hsp70 antibody into the cells inhibited SGLT1 activation. These results suggest that HS induces TGF-beta1 secretion, and then Hsp70 forms a complex with SGLT1 and increases the distribution of SGLT1 in the apical membrane. Next, we examined the effect of HS on plasma membrane integrity. Accumulation of calcein, a membrane-impermeable fluorescent dye, was decreased by HS and then returned to basal level. This recovery was inhibited by phloridzin, a selective SGLT inhibitor, and nonmetabolizable glucose analogues. Anti-TGF-beta1 antibody also inhibited the recovery of calcein accumulation. Taken together, the present results show that HS elevates SGLT1 activity mediated via the TGF-beta1 signaling pathway and that the increase in glucose uptake is necessary to repair plasma membrane injury.
authors.affiliation: Department of Environmental Biochemistry and Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ikari
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051269:Sodium-Glucose Transporter 1; D013312:Stress, Physiological; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005947:Glucose