Presenilins in the heart: presenilin-2 expression is increased by low glucose and by hypoxia in cardiac cells.
Cardiac cells are subjected to hypoxia in many cardiovascular diseases. We studied a broad spectrum of genes using a macroarrays-based method to analyze RNA of rat cardiac fetal cell line H9c2 after 4 h of hypoxic conditions in the incubator-1% oxygen concentration, as compared to normoxic conditions (21% oxygen). The cDNAs were prepared from total RNAs using Atlas Rat 1.2 Array (Clontech Laboratories) and hybridized to the membrane containing 1176 rat cDNAs and 9 housekeeping control cDNAs. Genes expression was analyzed using AtlasImage 1.01 software. We found over 45 genes up-regulated in a range of 1.5-2.9 times and 9 genes down-regulated to a range of 0.4-0.7 times, under hypoxia versus normoxia. Presenilin-2 (PS2) was detected in the cultured heart cells. RT-PCR confirmed the presence of PS2 in the heart of adult rats. Using quantitative real-time RT-PCR, we further studied the expression of presenilin-2 mRNA under conditions of low oxygen supply and glucose starvation. Glucose deprivation itself caused significant up-regulation of the presenilin-2 (to 160%) and with low oxygen increased presenilin-2 level to over 200% of the control. Presenilin-2 has previously been associated with intercellular signaling in the central nervous system, in Alzheimer's disease. The finding of presenilin-2 in the heart and the responsiveness to low glucose and hypoxia suggests that PS2 may be regulated by conditions of ischemia, a condition which both the heart and brain may experience.
Mohuczy
Dagmara
D
Department of Physiology, College of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. dag@college.med.ufl.edu
Qian
Keping
K
Phillips
M Ian
MI
D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D053766:Presenilin-2; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation
D018076:DNA, Complementary; D008565:Membrane Proteins; D053766:Presenilin-2; D012333:RNA, Messenger; D005947:Glucose