Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cross-talk between the two transcription factors, p53 and hypoxia inducible factor 1alpha (HIF1A), is important in different pathophysiological conditions (Hammond and Giaccia, 2006, Clin Cancer Res 12:5007-5009) such as in the transition from myocardial hypertrophy to cardiac dilatation and heart failure. In that context, p53 induces HIF1A degradation which in turn provokes the transition from compensatory hypertrophy to myocardial thinning and chamber dilatation (Sano et al., 2007, Nature 446:444-448). In order to investigate the mechanism of p53-induced HIF1A degradation, we used the established in vitro model of deferroxamine (DFX)-induced HIF1A accumulation in H9c2 cardiac cells (Sano et al., 2007, Nature 446:444-448). Here, we report that opposite to HIF1A accumulation following exposure to DFX, prolonged DFX-induced p53 activation and HIF1A protein decrease, without any change in Hif1a mRNA. HIF1A protein decrease accompanied upregulated HIF1A ubiquitination. MDM2, an ubiquitin E3 ligase target gene of p53, was upregulated following prolonged DFX, but using p53/Mdm2 double-null mouse embryonic fibroblasts, we found that p53 upregulated HIF1A ubiquitination and degradation independently of MDM2. Moreover, with prolonged DFX treatment, an enhanced interaction between MDM2 and HIF1A was lacking. Instead, phospho-Akt(ser473) was decreased during the phase coinciding with HIF1A degradation, and inhibition of PKB/Akt phosphorylation using PI3K inhibitor (LY294002) upregulated HIF1A ubiquitination. In summary, we propose that p53-induced HIF1A degradation is not exclusively MDM2-mediated, but reversible by PKB/Akt phosphorylation.
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PMID:PKB/Akt activation inhibits p53-mediated HIF1A degradation that is independent of MDM2. 1995 Feb 14

Introduction: Androgenetic alopecia is a common hair loss disorder affecting up to 80% of males by the age of 80. It is characterized by androgen related progressive thinning of hair in a defined pattern. It results in diminished self-esteem, reduced confidence and distress in affected men, irrespective of age or stage of baldness. An effective treatment for hair baldness is needed.Areas covered: In androgenetic alopecia, hair follicles undergo progressive miniaturization. Genetic factors and androgens are key role-players in disease pathogenesis. Herein the authors review the pharmacologic treatment of androgenetic alopecia, which involves 5 alpha reductase inhibitors, minoxidil and prostaglandins. Non-pharmacologic approaches are also explored.Expert opinion: Androgenetic alopecia progresses over time and although the current available medical treatments like finasteride and minoxidil are effective in arresting the progression of the disease, they allow only partial regrowth of hair at its best. Early treatment achieves a more optimal outcome. Non-pharmacologic treatments like PRP can be considered in patients refractory to medical treatment.Abbreviations: MPHL: male pattern hair loss; AGA: androgenetic alopecia; DHT: dihydrotestosterone; 5AR: 5-alpha-reductase; VEGF: vascular endothelial growth factor; PG's: prostaglandins (PG's); PGD2R: prostaglandin D2 receptor; VPA: valproic aid; SR: Serenoa Repens; PRP: platelet-rich plasma; PDGF: platelet derived growth factor; TGF: transforming growth factor; ERK: extracellular signal-regulated kinase; PKB: protein kinase B; LLLT: low-level laser therapy; ROS: reactive oxygen species; RCT: randomized control trial; SFRP1: secreted frizzled related protein 1; DP: dermal papilla; PDE5: phosphodiesterase 5.
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PMID:A review of the treatment of male pattern hair loss 3206 84