Recovery from heat shock injury by activation of Na+-glucose cotransporter in renal epithelial cells.
Exposure of cells or organs to sublethal physical or chemical stresses induces disruption of cellular structures and functions. Here, we examined whether Na(+)-glucose cotransporter (SGLT1) is involved in the recovery from heat shock (HS) injury in porcine renal epithelial LLC-PK(1) cells. Recovery from HS (42 degrees C for 3 h, then 37 degrees C for 12 h) increased SGLT1 activity, assessed by [14C]alpha-methyl glucopyranoside uptake, and a maximal transport rate (V(max)) from 2.4 to 5.9 nmol/mg protein/30 min, but did not alter an apparent affinity constant (K(m)). Protein distribution of SGLT1 in apical membrane fraction was also increased after recovery from HS without changing in total membrane fraction. Membrane integrity assessed by calcein accumulation was decreased by HS, and then returned to basal level. This recovery was inhibited by phloridzin, a potent SGLT1 inhibitor, and nonmetabolizable glucose analogues. Anti-transforming growth factor-beta 1 (TGF-beta 1) antibody inhibited both elevation of SGLT1 distribution in apical membrane and recovery of calcein accumulation induced by HS. Taken together, HS increases in the number of SGLT1 protein in apical membrane mediated via TGF-beta 1 signaling pathway. The increase of glucose uptake is necessary to repair plasma membrane integrity.
Ikari
Akira
A
Department of Environmental Biochemistry and Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, Shizuoka 422-8526, Japan. ikari@u-shizuoka-ken.ac.jp
Nakano
Mika
M
Ishibashi
Mihoko
M
Kawano
Kazuya
K
Suketa
Yasunobu
Y
Harada
Hitoshi
H
Takagi
Kuniaki
K
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D004847:Epithelial Cells / Q000378:metabolism*; D005452:Fluoresceins; D018869:Heat-Shock Response; D007668:Kidney / Q000166:cytology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1
D005452:Fluoresceins; D009004:Monosaccharide Transport Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007770:L-Lactate Dehydrogenase; C007740:fluorexon