Lack of trehalose accelerates H2O2-induced Candida albicans apoptosis through regulating Ca2+ signaling pathway and caspase activity.
Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H(2)O(2) treatment together with an increase of intracellular Ca(2+) level and caspase activity. When the intracellular Ca(2+) level was stimulated by adding CaCl(2) or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca(2+) pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H(2)O(2) treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H(2)O(2). Our results suggest that Ca(2+) and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H(2)O(2)-induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans.
School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
Hui
H
Lu
ZhenYu
Z
Zhu
LingLing
L
Dong
XinMing
X
Jia
XuanRong
X
Sun
Lan
L
Yan
YiFeng
Y
Chai
YuanYing
Y
Jiang
YingYing
Y
Cao
D017209:Apoptosis / Q000187:drug effects*; D019703:Calcineurin / Q000378:metabolism; D020013:Calcium Signaling; D002176:Candida albicans / Q000166:cytology* / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009154:Mutation; D018384:Oxidative Stress; D014199:Trehalose / Q000172:deficiency*
D014199:Trehalose; D006861:Hydrogen Peroxide; D019703:Calcineurin; D020169:Caspases
Curr Opin Microbiol. 2004 Dec;7(6):655-60
15556039
J Biol Chem. 2003 Aug 1;278(31):28831-9
12754197
J Cell Biol. 2005 Jan 17;168(2):257-69
15657396
J Cell Biol. 1999 May 17;145(4):757-67
10330404
Mol Microbiol. 2006 Mar;59(5):1429-51
16468987
Food Chem Toxicol. 2002 Jul;40(7):871-98
12065209
J Clin Microbiol. 1999 Dec;37(12):3896-900
10565903
Mol Biol Cell. 2004 Mar;15(3):1436-44
14718573
Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17326-31
16301538
Mol Microbiol. 2005 Nov;58(3):824-34
16238630
Infect Immun. 2004 Dec;72(12):7330-3
15557662
Curr Biol. 2004 May 4;14(9):R339-40
15120084
J Bacteriol. 1998 Aug;180(15):3809-15
9683476
J Cell Biol. 1997 Nov 3;139(3):729-34
9348289
Microbiology (Reading). 2007 Oct;153(Pt 10):3211-3217
17906120
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14327-32
14623979
Mol Microbiol. 2003 May;48(4):959-76
12753189
Physiol Rev. 2000 Oct;80(4):1483-521
11015619
J Med Microbiol. 2010 Feb;59(Pt 2):149-157
19892857
Microbiology (Reading). 2002 Aug;148(Pt 8):2599-2606
12177354
Cell Biochem Biophys. 1999;30(1):115-51
10099825
Transfusion. 2009 Oct;49(10):2158-66
19555421
Genes Dev. 1997 Dec 15;11(24):3432-44
9407035
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14463-8
16183741
Arch Microbiol. 2000 Oct;174(4):217-24
11081789
Glycobiology. 2003 Apr;13(4):17R-27R
12626396
Planta. 2003 Jul;217(3):517-22
12783227
Trends Biochem Sci. 1995 Jan;20(1):3-10
7878741
Microbiology (Reading). 2002 May;148(Pt 5):1281-90
11988502
Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):726-31
16407097
Mol Microbiol. 1999 Nov;34(4):792-8
10564518
J Cell Biol. 2005 Jun 6;169(5):711-7
15939758
Free Radic Biol Med. 2006 Apr 1;40(7):1201-9
16545688
Exp Eye Res. 2009 Sep;89(3):311-8
19345212
Fungal Genet Biol. 2009 Feb;46(2):183-9
19049890
Infect Immun. 2006 Jul;74(7):4366-9
16790813
Adv Dent Res. 2006 Apr 01;19(1):80-4
16672555
Infect Immun. 2002 Apr;70(4):1772-82
11895938
Mol Cell. 2002 Apr;9(4):911-7
11983181
Med Mycol. 2007 Jun;45(4):321-46
17510856
J Biol Chem. 2005 Apr 15;280(15):14691-9
15691845
Clin Microbiol Infect. 2007 Apr;13(4):384-94
17359322