Fetal and Placental Cyclic Inositol Phosphohydrolase in Normoxia and Hypoxia

Tan, Sidhartha; Sekar, Mahendran

doi:10.1159/000014031

Cited by 1 publication

(2 citation statements)

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Section: Downregulated Genesmentioning

confidence: 99%

“…Phospholipase C hydrolysis of phosphoinositide (PI) results in the generation of cyclic and noncyclic inositol phosphates (51). Cyclic inositol phosphohydrolase (cIPH) is a phosphodiesterase that cleaves the cyclic bond of one of the products of the phospholipase C reaction, cyclic inositol monophosphate (51). It has recently been purified from the human placenta and is identical to lipocortin III (51), a gene found to be markedly downregulated during cAMP treatment (Supplemental Table A) and during the window of implantation (28).…”

Section: Downregulated Genesmentioning

confidence: 99%

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Activation of the protein kinase A pathway in human endometrial stromal cells reveals sequential categorical gene regulation

Tierney

Tulač

Huang

et al. 2003

Physiological Genomics

102

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Decidualization of endometrial stromal cells is a prerequisite for human implantation and occurs in vivo in response to progesterone and involves activation of the protein kinase A (PKA) pathway. The objective of this study was to determine the molecular signatures and patterns of gene expression during stimulation of this pathway with an analog of cAMP. Endometrial stromal cells from two subjects were treated with or without 8-Br-cAMP (1 mM) for 0, 2, 12, 24, 36, and 48 h and were processed for microarray analysis, screening for 12,686 genes and ESTs. Most abundantly upregulated genes included neuropeptides, immune genes, IGF family members, cell cycle regulators, extracellular matrix proteases, cholesterol trafficking, cell growth and differentiation, hormone signaling, and signal transduction. Most abundantly downregulated genes included activator of NF-kappaB, actin/tropomyosin/calmodulin binding protein, cyclin B, IGFBP-5, alpha1 type XVI collagen, lipocortin III, l-kynurenine hydrolase, frizzle-related protein, and cyclin E2. RT-PCR validated upregulation of IGFBP-1, preprosomatostatin, and IL-11, and Northern analysis validated their kinetic upregulation. RT-PCR confirmed downregulation of IGFBP-5, cyclin B, and TIL-4. K-means analysis revealed four major patterns of up- and downregulated genes, and genes within each ontological group were categorized into these four kinetic patterns. Within each ontological group different patterns of temporal gene expression were observed, indicating that even genes within one functional category are regulated differently during activation of the PKA pathway in human endometrial stromal cells. Overall, the data demonstrate kinetic reprogramming of genes within specific functional groups and changes in genes associated with nucleic acid binding, cell proliferation, decreased G protein signaling, increased STAT pathway signaling, structural proteins, cellular differentiation, and secretory processes. These changes are consistent with cAMP modulating early events (0-6 h) primarily involving cell cycle regulation, subsequent events (12-24 h) involving cellular differentiation (including changes in morphology and secretory phenotype), and late events (24-48 h) mediating more specialized function, including immune modulators, in the human endometrial stromal cell.

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Section: Downregulated Genesmentioning

confidence: 99%