Apoptosis through Death Receptors in Temporal Lobe Epilepsy-Associated Hippocampal Sclerosis

Table 1

Array target genes: apoptosis through death receptors in TLE(HS).

Target genes
Symbol, approved name, and Assay ID	Synonyms and aliases	Function	RQ
ACTA1; actin, alpha 1, skeletal muscle; Hs00559403_m1	NEM3, “nemaline myopathy type 3”	Cell motility	1.12
ACTB; actin, beta; Hs99999903_m1		Cell motility	1.74
APAF1; apoptotic peptidase activating factor 1; Hs00559441_m1	APAF-1, CED4	Apoptosis induction by CASP3 activation	1.59
BAX; BCL2-associated X protein; Hs00180269_m1	BCL2L4	Apoptosis induction by CASP3 activation	1.50
BCL2; B-cell CLL/lymphoma 2; Hs99999018_m1	Bcl-2, PPP1R50, “protein phosphatase 1, and regulatory subunit 50”	Apoptosis inhibition	1.87
BID; BH3 interacting domain death agonist; Hs00609632_m1		Apoptosis induction	1.40
BIRC2; baculoviral IAP repeat containing 2; Hs01112284_m1	“Apoptosis inhibitor 1”, c-IAP1, cIAP1, hiap-2, MIHB, “NFR2-TRAF signalling complex protein”, and RNF48	Apoptosis inhibition	1.31
BIRC3; baculoviral IAP repeat containing 3; Hs00154109_m1	“Apoptosis inhibitor 2”, c-IAP2, cIAP2, hiap-1, “inhibitor of apoptosis protein 1”, MALT2, “mammalian IAP homolog C”, MIHC, RNF49, and “TNFR2-TRAF signaling complex protein”	Apoptosis inhibition	1.27
CASP2; caspase 2; Hs00234982_m1	ICH1, MGC2181, PPP1R57, and “protein phosphatase 1, regulatory subunit 57”	Involved in the activation cascade of caspases responsible for apoptosis execution	1.38
CASP3; caspase 3; Hs00234387_m1	Apopain, CPP32, CPP32B, and Yama	Involved in the activation cascade of caspases responsible for apoptosis execution	1.44
CASP7; caspase 7; Hs00169152_m1	CMH-1, ICE-LAP3, and MCH3	Involved in the activation cascade of caspases responsible for apoptosis execution; overexpression promotes programmed cell death	2.13
CASP8; caspase 8; Hs01018151_m1	Casp-8, FLICE, MACH, and MCH5	Most upstream protease of the activation cascade of caspases responsible for the FAS mediated and TNFRSF1A induced cell death	2.45
CASP9; caspase 9; Hs00154260_m1	APAF-3, ICE-LAP6, MCH6, PPP1R56, and “protein phosphatase 1, regulatory subunit 56”	Involved in the activation cascade of caspases responsible for apoptosis execution	1.55
CFLAR; CASP8 and FADD like apoptosis regulator; Hs01116280_m1	c-FLIP, CASH, Casper, CLARP, FLAME, FLIP, I-FLICE, and MRIT	Apoptosis regulator protein as FAS mediated apoptosis inhibitor	1.59
CHUK; conserved helix-loop-helix ubiquitous kinase; Hs00175141_m1	IKBKA, IKK-alpha, IKK1, IKKA, and NFKBIKA	Serine kinase. Essential role in the NFkB signaling pathway	1.22
DAXX; death-domain associated protein; Hs00154692_m1	DAP6	JNK pathway and apoptosis mediator via MAP3K5 [FAS and TGFBR2 (transforming growth factor beta receptor II) signaling]	1.53
DIABLO; diablo, IAP-binding mitochondrial protein; Hs00219876_m1	DFNA64, DIABLO-S, FLJ10537, FLJ25049, “second mitochondria-derived activator of caspase”, and SMAC	Apoptosis promoter by caspase activation in the cytochrome c/APAF1/CASP9 pathway	1.45
FADD; Fas associated via death domain; Hs00538709_m1	“Fas-associating death domain-containing protein,” “Fas-associating protein with death domain,” GIG3, “growth-inhibiting gene 3 protein,” “mediator of receptor-induced toxicity,” and MORT1	CASP8 and CASP10 apoptotic adaptor recruiter to activated FAS and TNFRSF1A	1.13
FAS; Fas cell surface death receptor; Hs00531110_m1	APO-1, CD95, and “TNF receptor superfamily member 6”	Receptor with death domain for FASLG	1.65
FASLG; Fas ligand; Hs00181225_m1	CD178, FasL	Cytokine ligand for FAS	5.46
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta; Hs00233287_m1	IKK-beta, IKK2, IKKB, and NFKBIKB	NFkB activator	1.96
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma; Hs00415849_m1	FIP-3, FIP3, Fip3p, IKK-gamma, NEMO, and ZC2HC9	NFkB activator	1.65
MAP3K5; mitogen-activated protein kinase kinase kinase 5; Hs00178726_m1	“Apoptosis signal regulating kinase 1,” ASK1, and MAPKKK5	Signal transduction mediator by oxidative stress and receptor-mediated inflammatory signals (TNF)	1.55
MAPK8; mitogen-activated protein kinase 8; Hs01548508_m1	JNK, JNK1, “JUN N-terminal kinase,” and SAPK1	Stressed cell apoptosis promoter through TP53 and YAP1	1.05
MAPK9; mitogen-activated protein kinase 9; Hs00177102_m1	JNK2, “Jun kinase,” p54a, and SAPK	Stressed cell apoptosis promoter through TP53 and YAP1	0.86
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; Hs00765730_m1	KBF1, NF-kappaB, NF-kB1, NFkappaB, NFKB-p50, p105, and p50	Rel protein-specific transcription inhibitor (105 kD) and DNA binding subunit of the transcription factor NFkB (50 kD)	1.50
NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100); Hs00174517_m1	LYT-10, NF-kB2, p105, and p52	Subunit of the transcription factor NFkB	3.21
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; Hs00153283_m1	IkappaBalpha, IKBA, and MAD-3	NFkB inhibitor	2.36
NGF; nerve growth factor (beta polypeptide); Hs01113193_m1		Ligand for NTRK1 and NGFR; neuronal proliferation, differentiation and survival regulator	0.90
NGFR; nerve growth factor receptor; Hs00609976_m1	CD271, “low affinity nerve growth factor receptor,” p75NTR, “TNFR superfamily, member 16,” and TNFRSF16	Neural cell death or survival mediator	3.53
PARP1; poly(ADP-ribose) polymerase 1; Hs00242302_m1	PARP	DNA repair pathway initiation; apoptosis promoter in response to genotoxic stress	1.51
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A; Hs00153294_m1	p65	Subunit of the transcription factor NFkB	2.02
TNF; tumor necrosis factor; Hs00174128_m1	DIF, “TNF superfamily, member 2,” TNF-alpha, and TNFSF2	Multifunctional proinflammatory cytokine ligand for TNFRSF1A and TNFRSF1B	39.96
TNFRSF10A; tumor necrosis factor receptor superfamily member 10a; Hs00269492_m1	Apo2, CD261, DR4, and TRAILR-1	Receptor with death domain for TNFSF10; NFkB activator	2.39
TNFRSF10B; tumor necrosis factor receptor superfamily member 10b; Hs00366278_m1	CD262, DR5, KILLER, TRAIL-R2, TRICK2A, and TRICKB	Receptor with death domain for TNFSF10; ER stress-induced apoptosis promoter; NFkB activator	1.55
TNFRSF10C; tumor necrosis factor receptor superfamily member 10c; Hs00182570_m1	CD263, DcR1, LIT, TRAILR3, and TRID	Decoy receptor for TNFSF10; apoptosis inhibitor	4.82
TNFRSF10D; tumor necrosis factor receptor superfamily member 10d; Hs00533560_m1	CD264, DcR2, TRAILR4, and TRUNDD	Decoy receptor for TNFSF10; apoptosis inhibitor	3.74
TNFRSF1A; tumor necrosis factor receptor superfamily member 1A; Hs00205419_m1	CD120a, TNF-R, TNF-R-I, TNF-R55, TNFAR, and TNFR60	Receptor with death domain for TNF and LTA (lymphotoxin alpha); NFkB activator, apoptosis mediator, and inflammation regulator	3.07
TNFRSF21; tumor necrosis factor receptor superfamily member 21; Hs00237054_m1	CD358, “death receptor 6,” and DR6	Receptor with death domain; apoptosis promoter	1.09
TNFRSF25; tumor necrosis factor receptor superfamily member 25; Hs00187070_m1	APO-3, DDR3, DR3, LARD, TR3, TRAMP, WSL-1, and WSL-LR	Receptor with death domain for TNFSF12; mediator of NFkB activation and apoptosis promoter	1.72
TNFRSF6B; tumor necrosis factor receptor superfamily member 6b; Hs00234356_m1	DcR3, DCR3, M68, and TR6	Decoy receptor for FASLG; apoptosis inhibitor	2.54
TNFSF10; tumor necrosis factor superfamily member 10; Hs00174664_m1	Apo-2L, CD253, TL2, and TRAIL	Cytokine ligand for TNFRSF10A, TNFRSF10B, TNFRSF10C, and TNFRSF10D	2.50
TP53; tumor protein p53; Hs01034249_m1	LFS1, “Li-Fraumeni syndrome,” and p53	Tumor suppressor, growth arrest, or apoptosis promoter depending on the physiological circumstances and cell type	2.77
TRAF2; TNF receptor associated factor 2; Hs00184192_m1	TRAP3	Mediator of the antiapoptotic signals from TNF receptors; NFkB and JNK activation regulator	1.54

List of all target genes investigated in the array, involved in the extrinsic apoptotic pathway. The gene expression data [relative quantification (RQ) column], also shown in Figure 1, corresponds to the cDNA pooled from TLE(HS) patients () versus the cDNA pooled from post mortem controls (). The latter was used as a calibrator with gene expression equal to 1.0. The values in the table can be converted to fold change values, where the negative inverse (−1/) is taken for values between 0 and 1 (e.g., 0.5 is converted to −2). Values greater than 1 will not be affected. A −2 value indicates that the molecule is 2-fold downregulated. Only MAPK9 and NGF were downregulated. The reference gene candidates in the plate were 18S (eukaryotic 18S rRNA; Hs99999901_s1), GAPDH (glyceraldehyde-3-phosphate dehydrogenase; Hs99999905_m1), GUSB (glucuronidase, beta; Hs99999909_m1), and HPRT1 (hypoxanthine phosphoribosyltransferase 1; Hs99999908_m1) although only GAPDH and HPRT1 were effectively used as reference genes (in combination).