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General Comment |
Deregulation of apoptosis is responsible for a wide range of diseases such as autoimmune and neurodegenerative disorders. By sequence homology searches using the catalytic domains of 2 serine/threonine kinases important in the regulation of apoptosis, DAP kinase (600954) and ZIP kinase (603289), Sanjo et al. (1998) cloned 2 novel members of the ser/thr protein kinase family, which they termed DRAK1 (604726) and DRAK2, but which were later designated STK17A and STK17B, respectively.
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Comment |
Identification of Genes Involved in Apoptosis and Dominant Follicle Development During Follicular Waves in Cattle.
Evans AC, et al 2004 hypothesize that granulosa and theca cells from growing dominant follicles, with relatively high intrafollicular concentrations of estradiol, have a greater expression of genes involved in inhibiting apoptosis pathways and lower expression of genes involved in apoptosis pathways than growing subordinate follicles with lower estradiol concentrations. Using the well-characterized bovine dominant follicle model, they collected granulosa and theca cells from individual dominant and the largest subordinate follicle 3 days after initiation of a follicular wave in four animals. Based on ultrasound analysis, both follicle types were in the growth phase at the time of ovariectomy. However, dominant follicles were larger (9.8+/-1.0 versus 7.6+/-0.6 mm in diameter, P<0.05) and had greater intrafollicular concentrations of estradiol ( P<0.05) compared with the largest subordinate follicles. They used bovine cDNA microarrays, which contained a total of 1400 genes including a subset of 53 genes known to be involved in apoptosis pathways, to determine which apoptosis and marker genes from each of the four dominant versus subordinate follicles were potentially differentially expressed. Using a low stringency-screening criterion, 22 genes were identified. Quantitative real-time PCR confirmed that 16 of these genes were differentially expressed. The high intrafollicular concentrations of estradiol in growing dominant follicles were positively associated with enhanced expression of mRNAs in granulosa cells for aromatase, LH receptor, estradiol receptor beta, DICE-1 and MCL-1 compared with granulosa cells from subordinate follicles (all survival-associated genes). In contrast, the relatively low intrafollicular concentrations of estradiol in growing subordinate follicles were positively associated with enhanced expression of mRNAs in granulosa cells for beta glycan, COX-1, TNFalpha, CAD and DRAK-2, and in theca cells for beta glycan, caspase 13, P58(IPK), Apaf-1, BTG-3, and TS-BCLL compared with granulosa or theca cells from dominant follicles (genes that are all associated with cell death and/or apoptosis). These genes may be candidate estradiol target genes and that they may be early markers for the final stages of follicle differentiation and initiation of apoptosis and thus selection of dominant follicles during follicular waves.
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