Table 4 A list of differentially expressed proteins in the hippocampus with fundamental roles in the regulation of cell death

F1LMM8

Q64536

Pdk2

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial

–

↓ (0.46)

–

–

–

p53 activation decreases Pdk2 transcription [92]

P97570

Pla2g6

85/88 kDa calcium independent phospholipase A2

S

–

C

–

M

tBID and Bax augments Pla2g6 (iPLA2) activity via ROS production leading to changes in the MOM [93]

Overexpression of iPLA2 increased the rate of apoptosis, iPLA2 is cleaved by caspase-3 [94]

β-cell apoptosis is attributable to the modulation of 5′SS selection in Bcl-X pre-mRNA by bioactive lipids modulated by iPLA2 [95]

G3V8Q9

A0A0G2K8G0

P70478

Apc

Adenomatosis polyposis coli

–

C

–

–

F

APC can regulate apoptosis by governing the level of caspase-3 [133]

P23928

Cryab

Alpha-crystallin B chain

C

–

–

–

–

Cryab prevents apoptosis; it binds to caspase-3 [134], Bax and Bcl-X_S [135] and p53 [136]

Cryab gene is a targer of p53 and p53-dependent apoptosis is affected by Cryab expression [137]

G3V8T9

Q9JKL3

Q63690

Bax

Apoptosis regulator BAX

–

S

C

F

M

Pro-apoptotic member of Bcl-2 family, its activation permeabilizes the MOM during apoptosis [96]

Deletion of Bax is sufficient to inhibit apoptosis [97]

Bax is cleaved by active calpains [80]

E9PST5

Acin1

Apoptotic chromatin condensation inducer 1

–

↑ (2.02)

↓ (0.36)

–

↑ (3.30)

Acin1 can induce apoptotic chromatin condensation after its cleavage by caspase-3 [137]

Q91XJ1

Becn1

Beclin-1

N

C

C

–

N

Beclin-1-induced autophagy is inversely correlated with apoptosis [13]

Q6IN33

Rcan1

Calcipressin-1

–

C

S

M

F

Calcineurin regulation [138]; Rcan1 absence enhances calcineurin activity and Fas ligand expression [98]

A0A0G2JSK3

Q8CH27

Rcan2

Calcipressin-2

S

N

S

N

F

Calcineurin regulation [138]

P48199

A0A0G2K8V5

Crp

C-reactive protein

C

–

–

–

–

Crp can induce the upregulation of p53 and increase caspase-3 activity [139]

F1MAJ0

A0A0G2JY48

Ephb2

Eph receptor B2

–

S

C

F

M

Ephb2 can prevent against Fas-triggered apotosis by inhibition of caspase-8 and caspase-3 [140]

Q8R2E7

Fadd

FAS-associated death domain protein

S

C

–

–

F

Pro-apoptotic adapter protein involved in extrinsic pathway of apoptosis [100]

Overexpression of FADD promotes apoptosis [103]

Q63226

F1LXB6

Grid2

Glutamate ionotropic receptor, delta-2

N

N

C

F

–

Gain-to-function mutation of Grid2 induces neuronal death [105]; this mutation is associated with increased expression of Bax, Bcl-X_S, caspase-3 and -8 [106]

TNF-α has a role in regulation of Grid2 gene expression, which can be a suppressor in TNF-induced neurodegeneration [107]

G3V913

P42930

Hspb1

Heat shock 27 kDa

–

↑ (2.14)

↑ (2.39)

–

–

Hspb1 indirectly suppresses stress-induced Bax oligomerization and translocation to mitochondria; it can inhibit caspase-3 activity [141]

Hspb1 can mediate Bad inactivation [142]

Q8VH49

Higd1a

HIG1 domain family 1A, mitochondrial

C

N

C

F

N

Higd1a is a survival factor and is associated with caspase-3 activation [109, 110]

P31423

Grm4

Metabotropic glutamate receptor 4

S

S

N

N

M

Decreased expression of GRM4 gene is associated with apoptosis of cerebellar granule neurons [86]

Activation of Grm4 can activate pro-caspase 8/9/3 and disrupt the balance of Bcl-2/Bax expression [113]

A0A0G2JZT0

Q64663

P2rx7

P2X purinoceptor 7

S

–

–

–

–

P2rx7s mediate caspase-8 and caspase-3 dependent apoptosis [115]

Its activation is associated with Ca²⁺ responses and TNF-α production [116,117,118]

P27008

Parp1

Poly [ADP-ribose] polymerase 1

–

C

–

–

F

Parp1 is cleaved by caspase-3 [21]

F1LNG8

Q5BK62

Mpv17

Protein Mpv17

–

N

–

F

F

The increase of Mpv17 expression can be accompanied by the enhanced expression of p53, Bax, cyt c and active caspase-3 and decreased expression of Bcl-2 in the pathological proces [119]

P70600

Ptk2b

Protein-tyrosine kinase 2-beta

–

↓ (0.49)

–

–

–

Overexpression of Ptk2b can induce apoptosis [143]

B1WC67

Slc25a24

RCG29001

S

–

C

–

M

A survival factor, knock-down of Slc25a24 led to reduction of Ca²⁺ buffering capacity and sensitized cellts to cell death induced by mitochondrial permeability transition [120]

Q63639

Aldh1a2

Retinal dehydrogenase 2

N

S

S

N

–

Aldh1a2 mediates conversion of retinol into active retinoic acid, which the expression of Bcl-2, Bax, Bid, caspase-8 and -3 [122]

D4ADQ1

Rrm2b

Ribonucleotide reductase M2 B (TP53 inducible)

–

N

C

F

N

Loss of Rrm2b can increase apoptosis [123]

Rrm2b expression is induced by stress [124]

Rrm2b cleavage is mediated by caspase-8 and -3 [125]

P70501

A0A0G2K3S6

Rbm10

RNA-binding protein 10

–

N

–

F

F

Rbm10 knock-down can decrease caspase activation [126]

Rbm10 regulates alternative splicing of Fas and Bcl-X genes [127]

Rbm10 expression is associated with increased apoptosis [128]

A0A0G2JXI4

P52632

Stat5b;Stat5a

Signal transducer and activator of transcription

–

–

S

M

–

Stat5 regulate expression of Bcl-2 and Bcl-X_L and the level of caspase-3 [129,130,131]

F1M5H6

D4A6A8

A0A0G2KB61

Tp53bp2

Tumor protein p53-binding protein 2

–

S

N

N

M

Tp53bp2 binds to p53 and Bcl-2; it can alter p53 protein conformation and enhance the binding activity of p53 to the promotes of Bax [132]