Saturday, November 28, 2009

PKR

EIF2a-p is important for PKR inhibition of Cyclin D1.

Double-stranded RNA-dependent protein kinase regulates insulin-stimulated chondrogenesis in mouse clonal chondrogenic cells, ATDC-5.

"Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein that has been identified and characterized as a translational inhibitor in an interferon-regulated antiviral pathway. PKR inactivation suppresses osteoblast calcification and osteoclast formation. PKR is required for the in vitro differentiation of the mouse clonal chondrogenic cell line ATDC-5. ATDC-5 cells treated with insulin differentiated into chondrocytes and produced an alcian-blue-positive cartilage matrix. The protein expression of signal transducers and activators of transcription (STAT) peaked at day 7 of differentiation, whereas the expression of SRY-box-containing gene 9 (Sox-9), which is a transcription factor for chondrocyte differentiation, increased gradually. When the cells were treated with a PKR inhibitor (2-aminopurine), the cartilage matrix formation decreased. The protein expression of STAT1{Stat1 interacts with Cyclin D1} continued to increase up to day 21, whereas the expression of Sox-9 was low and did not increase. PKR was localized to a marginal region of the mandibular condyle cartilage in mouse embryos. PKR has important functions in the differentiation of chondrocytes through the modulation of STAT1 and Sox-9 expression."

Since PKR is important to chondroinduction maybe EIF2a-p and therefore Salubrinal are too.

"PKR/eIF-2α cascade has been implicated as a general transducer of apoptosis"

"2-Aminopurine (2-AP), which interacts with the ATP-binding site of PKR, is a potent inhibitor of PKR  and blocks tumor necrosis factor-α (TNF-α) and C2-ceramide [activities]"

"ATDC-5 cells show characteristics of undifferentiated prechondrogenic cells in the growth phase and maintain a potential for chondrogenesis. When treated with insulin, ATDC-5 cells undergo cellular condensation in the post-confluent phase and acquire the phenotype of chondrocytes, i.e., proteoglycan synthesis and type II collagen expression"

"the level of STAT1 protein was higher in the cells treated with insulin, especially at day 7 of culture and inhibition of PKR resulted in the sustained expression of STAT1. PKR interacts with STAT1 and PKR-STAT1 complexes interfere with the transactivation capacity"

"PKR inhibition sustains STAT expression, which results in the inhibition of chondrogenesis."

No comments:

Post a Comment