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Joy Jones

Publications and source records attributed to Joy Jones.

5 recordsLinked to original sources
PubMed2004

Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species.

During inflammation, NF-kappaB transcription factors antagonize apoptosis induced by tumor necrosis factor (TNF)alpha. This antiapoptotic activity of NF-kappaB involves suppressing the accumulation of reactive oxygen species (ROS) and controlling the activation of the c-Jun N-terminal kinase (JNK) cascade. However, the mechanism(s) by which NF-kappaB inhibits ROS accumulation is unclear. We identify ferritin heavy chain (FHC)--the primary iron storage factor--as an essential mediator of the antioxidant and protective activities of NF-kappaB. FHC is induced downstream of NF-kappaB and is required to prevent sustained JNK activation and, thereby, apoptosis triggered by TNFalpha. FHC-mediated inhibition of JNK signaling depends on suppressing ROS accumulation and is achieved through iron sequestration. These findings establish a basis for the NF-kappaB-mediated control of ROS induction and identify a mechanism by which NF-kappaB suppresses proapoptotic JNK signaling. Our results suggest modulation of FHC or, more broadly, of iron metabolism as a potential approach for anti-inflammatory therapy.

Apoptosis↗
PubMed2004

Short stature with normal growth hormone stimulation testing: lack of evidence for partial growth hormone deficiency or insensitivity.

OBJECTIVES: To test the hypothesis that children with short stature and peak stimulated GH (pGH) of 7-10 microg/l have partial GH deficiency and to test the hypothesis that short children with normal pGH but low IGF-I levels have partial GH deficiency or partial GH insensitivity. DESIGN AND PATIENTS: Retrospective analysis of the clinical and biochemical profiles of 76 children who underwent an evaluation for short stature (height < 5th percentile) that included two, sex steroid-primed GH stimulation tests. RESULTS: Patients with pGH < 7 microg/l (n = 14) differed significantly from those with pGH > 7 microg/l (n = 62), having greater midparental height (MPH) SDS, a greater disparity between height SDS and MPH SDS, and lower IGF-I SDS. Patients with pGH of 7-10 microg/l (n = 12) did not have characteristics intermediate between those with pGH < 7 microg/l and those with pGH > or = 10 microg/l, but instead resembled those with pGH > or = 10 microg/l. Patients with pGH > or = 7 microg/l, but low IGF-I (< -2 SDS) (n = 5), did not show characteristics intermediate between those with pGH < 7 microg/l and those with pGH > or = 7 microg/l and normal IGF-I. CONCLUSIONS: These data do not support either the hypothesis that children with pGH of 7-10 microg/l have partial GH deficiency or the hypothesis that children with normal pGH but subnormal IGF-I levels have partial GH deficiency or insensitivity.

Adolescent↗
PubMed2002

Regulation of the gadd45beta promoter by NF-kappaB.

In addition to coordinating immune and inflammatory responses, NF-kappaB/Rel transcription factors control cell survival. The NF-kappaB antiapoptotic function is crucial to oncogenesis, cancer chemoresistance, and to antagonize tumor necrosis factor (TNF) receptor-induced killing. Recently, we have shown that the suppression of the c-Jun-N-terminal kinase (JNK) cascade is a pivotal protective mechanism by NF-kappaB, and that this suppression involves the upregulation of gadd45beta/myd118. Induction of gadd45beta by stress and cytokines requires NF-kappaB; however, the regulatory mechanisms underlying this induction are not known. Here, we report that, in HeLa cells, the NF-kappaB subunit RelA is sufficient to activate gadd45beta expression, whereas Rel and p50 are not. Activation of gadd45beta by RelA depends on three kappaB elements at positions -447/-438 (kappaB-1), -426/-417 (kappaB-2), and -377/-368 (kappaB-3) of the gadd45beta promoter. Each of these sites binds to NF-kappaB complexes in vitro, and is required for optimal promoter transactivation. The data establish the direct participation of NF-kappaB in the regulation of Gadd45beta, thereby providing important mechanistic insights into the control of apoptosis by the transcription factor.

Animals↗