Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.2 (PDK1)
 2,238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we examined the modulatory effect of hinokitiol (HK) on the production of tumor necrosis factor (TNF)-alpha, a critical factor involved in skin inflammation and hair follicle apoptosis. HK effectively suppressed TNF-alpha production in lipopolysaccharide (LPS)-activated, macrophage-like (RAW264.7) cells. This compound also diminished mRNA synthesis of TNF-alpha, indicating that HK-mediated inhibition may occur at the transcriptional level. Moreover, this compound down-regulated the phosphorylation of PDK1, Akt/PKB, and ERK, resulting in a loss of nuclear factor (NF)-kappaB activation, which is detectable by immunoblotting and reporter gene assays. Therefore, these results suggest that HK may cure hair loss by suppressing factors that promote follicular apoptosis, such as TNF-alpha, in addition to stimulating new hair growth.
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PMID:Hinokitiol, a natural tropolone derivative, inhibits TNF-alpha production in LPS-activated macrophages via suppression of NF-kappaB. 1853 78

A monofunctional analog of the chemical warfare agent sulfur mustard (HD), 2-chloroethyl ethyl sulfide (CEES), induces tissue damage similar to HD. Herein we studied the molecular mechanisms associated with CEES-induced skin inflammation and toxicity in SKH-1 hairless mice. Topical CEES exposure caused an increase in oxidative stress as observed by enhanced 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrroline N-oxide protein adduct formation and an increase in protein oxidation. The CEES-induced increase in the formation of 8-oxo-2-deoxyguanosine indicated DNA oxidation. CEES exposure instigated an increase in the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38). After CEES exposure, a significant increase in the phosphorylation of Akt at Ser473 and Thr308 was observed as well as upregulation of its upstream effector, PDK1, in mouse skin tissue. Subsequently, CEES exposure caused activation of AP-1 family proteins and the NF-kappaB pathway, including phosphorylation and degradation of IkappaBalpha in addition to phosphorylation of the NF-kappaB essential modulator. Collectively, our results indicate that CEES induces oxidative stress and the activation of the transcription factors AP-1 and NF-kappaB via upstream signaling pathways including MAPKs and Akt in SKH-1 hairless mouse skin. These novel molecular targets could be supportive in the development of prophylactic and therapeutic interventions against HD-related skin injury.
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PMID:Sulfur mustard analog induces oxidative stress and activates signaling cascades in the skin of SKH-1 hairless mice. 1976 30