title: Hypoxia-inducible factor-1α regulates the expression of L-type voltage-dependent Ca(2+) channels in PC12 cells under hypoxia.
abstract: Hypoxia is an important factor in regulation of cell behavior both under physiological and pathological conditions. The mechanisms of hypoxia-induced cell death have not been completely elucidated yet. It is well known that Ca(2+) is critically related to cell survival. Hypoxia-inducible factor-1α (HIF-1α) is a core regulatory factor during hypoxia, and L-type voltage-dependent Ca(2+) channels (L-VDCCs) have been reported to play a critical role in cell survival. This study was conducted to explore the relationship between L-VDCC expression and HIF-1α regulation in PC12 cells under hypoxia. PC12 cells were treated at 20 or 3 % O2 to observe its proliferation and the intracellular calcium concentration. Then, we detected the protein expression of HIF-1α and L-VDCCs subtypes, Cav1.2 and Cav1.3. At last, to verify the relationship between HIF-1α and Cav1.2 and Cav1.3, we got the expression of Cav1.2 and Cav1.3 with Western blot and luciferase report gene assays after PC12 cells were treated by echinomycin, which is an HIF-1α inhibitor. Compared with 20 % O2 (normoxia), 3 % O2 (hypoxia) inhibited cell proliferation, increased the intracellular calcium concentration, and induced protein expression of HIF-1α. The protein expression of two L-VDCCs subtypes expressed in the nervous system, Cav1.2 and Cav1.3, was upregulated by hypoxia and reduced dose dependently by treatment with echinomycin, a HIF-1α inhibitor. Luciferase report gene assays showed that the expression of Cav1.2 and Cav1.3 genes was augmented under 3 % O2. However, echinomycin only slightly and dose dependently decreased expression of the Cav1.2 gene, but not that of the Cav1.3 gene. These data indicated that Cav1.2 might be regulated by HIF-1α as one of its downstream target genes and involved in regulation of PC12 cells death under hypoxia.
authors: Department of Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, 10# You An Men, Beijing, 100069, People's Republic of China.
authors: Ran
authors: R
authors: Li
authors: Yong
authors: Y
authors: Wang
authors: Zhaofei
authors: Z
authors: Yang
authors: Yunling
authors: Y
authors: He
authors: Tong
authors: T
authors: Zhao
authors: Ming
authors: M
authors: Fan
authors: Xuan
authors: X
authors: Wang
authors: Lingling
authors: L
authors: Zhu
authors: Xiaomin
authors: X
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism; D020013:Calcium Signaling; D015687:Cell Hypoxia; D049109:Cell Proliferation; D015870:Gene Expression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D015533:Transcriptional Activation
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C419385:L-type calcium channel alpha(1C); C093712:Cacna1d protein, rat
references: Comp Biochem Physiol B Biochem Mol Biol. 2001 Feb;128(2):187-204
references: 11207433
references: Neuroscience. 2008 Jun 23;154(2):473-81
references: 18502590
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11024-31
references: 11572963
references: Stroke. 2002 Jun;33(6):1706-11
references: 12053015
references: FASEB J. 2002 Aug;16(10):1151-62
references: 12153983
references: Brain Res Mol Brain Res. 2003 Feb 20;110(2):193-202
references: 12591156
references: J Biol Chem. 2003 Jun 20;278(25):22316-24
references: 12679337
references: Endocr Pathol. 2003 Winter;14(4):277-91
references: 14739486
references: J Neurochem. 2004 Feb;88(4):878-84
references: 14756808
references: Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424-8
references: 1065897
references: Nature. 1993 Sep 9;365(6442):153-5
references: 8371757
references: Nature. 1998 Jul 30;394(6692):485-90
references: 9697772
references: Cancer Res. 2005 Oct 1;65(19):9047-55
references: 16204079
references: Philos Trans R Soc Lond B Biol Sci. 2005 Dec 29;360(1464):2247-54
references: 16321794
references: J Physiol. 2008 Jul 1;586(Pt 13):3043-54
references: 18467365
references: PLoS One. 2008;3(7):e2718
references: 18648507
references: PLoS One. 2008;3(12):e4077
references: 19115003
references: Eur J Pharmacol. 2009 Jan 14;602(2-3):238-44
references: 19070614
references: Cell Stress Chaperones. 2009 Mar;14(2):183-92
references: 18726712
references: Mol Cell. 2009 Mar 13;33(5):627-38
references: 19285945
references: Exp Mol Med. 2009 Apr 30;41(4):269-76
references: 19299916
references: Curr Opin Neurobiol. 2009 Jun;19(3):237-44
references: 19559597
references: PLoS One. 2010;5(1):e8575
references: 20052410
references: Cell Calcium. 2010 Feb;47(2):183-9
references: 20080301
references: Cell Calcium. 2010 Feb;47(2):122-9
references: 20167368
references: Cell Calcium. 2010 Mar;47(3):264-72
references: 20061018
references: Basic Clin Pharmacol Toxicol. 2010 May;106(5):396-405
references: 20030631
references: Neurosci Lett. 2010 Jul 12;478(3):156-60
references: 20466036
references: PLoS One. 2011;6(6):e20423
references: 21674052
references: Eur J Neurosci. 2011 Aug;34(3):437-47
references: 21722208
references: Cell Death Differ. 2012 Feb;19(2):284-94
references: 21818118
references: Artif Cells Blood Substit Immobil Biotechnol. 2012 Feb;40(1-2):142-5
references: 22082349
references: Exp Cell Res. 2012 Aug 1;318(13):1480-91
references: 22510436
references: CNS Neurosci Ther. 2013 Mar;19(3):183-90
references: 23441691
references: Cell Death Differ. 2001 Apr;8(4):367-76
references: 11550088
references: Neurobiol Aging. 2006 Mar;27(3):439-45
references: 16464656
references: Circ Res. 2006 Jun 23;98(12):1528-37
references: 16709899
references: Cell Death Differ. 2007 Apr;14(4):775-84
references: 17039248
references: Genes Dev. 2000 Aug 15;14(16):1983-91
references: 10950862
references: Nat Neurosci. 2007 May;10(5):559-67
references: 17396124
references: J Neurosci. 2007 Jun 6;27(23):6320-32
references: 17554006
references: Can J Physiol Pharmacol. 2007 Jun;85(6):621-7
references: 17823624
references: Cell Death Differ. 2008 Apr;15(4):678-85
references: 18259193
references: Cell Death Differ. 2008 Apr;15(4):628-34
references: 18259197
references: Cell Death Differ. 2008 Apr;15(4):686-90
references: 18259200
references: FEBS J. 2008 Apr;275(8):1824-34
references: 18341590
references: J Biol Chem. 2013 May 3;288(18):12459-68
references: 23508951