The Effects of Venlafaxine and Dexamethasone on the Expression of HSP70 in Rat C6 Glioma Cells.
OBJECTIVE
The present study aimed to determine the intracellular action of the antidepressant, venlafaxine, in C6 glioma cells using heat shock protein 70 (HSP70) immunocytochemistry and HSP70 Western blots; HSP70 is known to be associated with stress and depression.


METHODS
The extent of HSP70 expression was measured after rat C6 glioma cells were treated with 1) dexamethasone only, 2) venlafaxine only, 3) simultaneous venlafaxine and dexamethasone, or 4) dexamethasone after venlafaxine pretreatment. Dexamethasone (10 microM, 6 hours) did not affect the level of HSP70 expression relative to control.


RESULTS
Short-term (1 hour) venlafaxine treatment significantly increased the level of HSP 70 expression. Simultaneous long-term (72 hours) venlafaxine and dexamethasone treatment significantly reduced the level of HSP70 expression. Dexamethasone treatment administered following long-term (24 and 72 hours) pretreatment with venlafaxine also significantly reduced the level of HSP70 expression.


CONCLUSIONS
Short-term treatment with venlafaxine increases the expression of HSP70, but prolonged treatment with dexamethasone suppresses the venlafaxine-induced expression of HSP70. These findings suggest that HSP70 and dexamethasone play a significant role in the pathophysiology of depression.
Yu
Jaehak
J
Department of Neuropsychiatry, Konkuk University School of Medicine, Seoul, Korea.
Roh
Sungwon
S
Lee
Jun-Seok
JS
Yang
Byung-Hwan
BH
Choi
Mi Ran
MR
Chai
Young Gyu
YG
Kim
Seok Hyeon
SH
J Biol Chem. 2000 Jul 21;275(29):22597-604
10781595
J Neurosci Res. 1990 Nov;27(3):360-73
2097380
Comp Biochem Physiol B Biochem Mol Biol. 2001 Jun;129(2-3):679-85
11399505
J Pharm Pharmacol. 1996 Jan;48(1):115-6
8722508
J Biol Chem. 2000 Aug 25;275(34):26058-65
10862623
Trends Neurosci. 1999 Mar;22(3):97-9
10199631
Physiol Res. 1997;46(2):161-4
9727508
Neurosci Lett. 2005 Dec 9;389(3):173-7
16115734
Neurochem Res. 2007 Mar;32(3):497-505
17268845
Biochem Biophys Res Commun. 1996 Feb 27;219(3):745-52
8645252
J Biol Chem. 1992 Nov 5;267(31):21987-90
1429548
Arch Gen Psychiatry. 1997 Jul;54(7):597-606
9236543
N Engl J Med. 1988 Aug 18;319(7):413-20
3041279
Clin Chim Acta. 2003 Jun;332(1-2):133-7
12763290
Biochem Biophys Res Commun. 1999 Aug 2;261(2):541-5
10425221
Biol Psychiatry. 2008 Feb 15;63(4):398-405
17825799
Int J Immunopharmacol. 1997 Nov-Dec;19(11-12):645-54
9669204
J Neurochem. 1995 Feb;64(2):724-32
7830066
Sci Am. 1993 May;268(5):56-64
8097593
Mol Pharmacol. 1997 Oct;52(4):571-81
9380019
J Neurosci. 2000 Jun 1;20(11):4030-6
10818138
Cell Stress Chaperones. 2000 Apr;5(2):76-86
11147968
Cancer Res. 1995 Dec 1;55(23):5512-9
7585624
Neuroscience. 1995 Nov;69(1):83-8
8637635
Science. 1996 Aug 9;273(5276):749-50
8701325
Stress. 1996 Jul;1(1):1-19
9807058
Neurosci Lett. 2003 May 22;342(3):206-10
12757900
J Biol Chem. 1996 Nov 29;271(48):30847-57
8940068
J Neurosci. 1996 Apr 1;16(7):2365-72
8601816
Neurosci Lett. 2004 Nov 30;372(1-2):99-103
15531096
Endocr Rev. 1996 Apr;17(2):187-205
8706631
J Neurochem. 1987 Jul;49(1):282-9
3035098
Biol Psychiatry. 2000 May 1;47(9):836-41
10812043
Mol Psychiatry. 1996 Sep;1(4):336-42
9118360
Annu Rev Genet. 1993;27:437-96
8122909
Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1091-7
10749702
J Clin Psychiatry. 1996;57 Suppl 13:49-55; discussion 56-8
8970504