Conversely, thapsigargin (an ERS inducer) increased the expression of PERK, eIF2a
, IRE-1, XBP-1, and factors involved in lipogenesis.
The HSV ICP34.5 protein dephosphorylates eIF-2[alpha], thus counteracting eIF2a
phosphorylation-induced autophagy [142-146].
The role of eIF2[alpha] phosphorylation in murine IECs was studied using mice with IEC-specific expression of nonphosphorylatable eIF2a
Wood et al., "ER stress signalling through eIF2a
and CHOP, but not IRE1a, attenuates adipogenesis in mice," Diabetologia, vol.
Kitamura, "Intervention in genotoxic stress-induced senescence by cordycepin through activation of eIF2a
and suppression of Sp1," Toxicological Sciences, vol.
To further analyze ER stress, expression of eIF2a
(Figure 8(c)), BIP (Figure 8(d)), CHOP (Figure 8(e)), and PERK (Figure 8(f)) was investigated by RT-PCR.
Activation of GRP78 enabled dimerization of PERK and its consequent autophosphorylation and then phosphorylated downstream eIF2a
. Both phosphorylated PERK and eIF2a
were inhibited by vitamin D treatment.
Increased GRP78/BiP expression was accompanied by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2a
Merrick, "Characterization of mammalian eIF2A
and identification of the yeast homolog," Journal of Biological Chemistry, vol.
Antibodies recognizing the following proteins were used in this study: caspase-3, [alpha]-SMA, and E-cadherin, Bax, Bcl-2, BIP, ATF-4, CHOP, P-eIF2a, and eIF2a
(Cell Signaling Technology); IL-1[beta], IL-1[beta], collagen I, fibronectin, CD11b, F4/80 (Abcam); Ly6G (Protein Specialists); and caspase 1 (Santa Cruz Biotechnology, Santa Cruz, CA, USA).
Anderson, "Hydrogen peroxide induces stress granule formation independent of eIF2a
phosphorylation," Biochemical and Biophysical Research Communications, vol.