Epidermal cytochrome

LOX-dependent superoxide production was also registered under ex vivo conditions [55]. It has been shown that the intravenous administration of lipopolysaccharide to rats stimulated superoxide production by alveolar and peritoneal macrophages. O Donnell and Azzi [56] proposed that a relatively high rate of superoxide production by cultured human fibroblasts in the presence of NADH was relevant to 15-LOX-catalyzed oxidation of unsaturated acids and was independent of NADPH oxidase, prostaglandin H synthase, xanthine oxidase, and cytochrome P-450 activation or mitochondrial respiration. LOX might also be involved in the superoxide production by epidermal growth factor-stimulated pheochromo-cytoma cells [57]. 

Constitutive activation of the P13-K - Akt/PKB survival signaling pathway is a likely mechanism by which many cancers become refractory to cytotoxic therapy. In LNCaP prostate cancer cells, the PTEN is inactivated, leading to constitutive activation of Akt/PKB and resistance to apoptosis. However, apoptosis and inactivation of Akt/PKB can be induced in these cells by treatment with P13-K inhibitors. Surprisingly, androgen, epidermal growth factor, or semm can protect these cells from apoptosis, even in the presence of P13-K inhibitors and without activation of Akt/PKB, indicating the activity of a novel, Akt/PKB-independent survival pathway. This pathway blocks apoptosis at a level prior to caspase 3 activation and release of cytochrome c from mitochondria (Carson et al, 1999)... 

Boerner JL, Demory ML, Silva C et al. Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II. Mol Cell Biol 2004 24 7059-7071. 

Further evidence that oenocytes are the cell type involved in hydrocarbon production was obtained by Wicker-Thomas et al. (unpublished data). The enzyme involved in the final step in hydrocarbon production, a cytochrome P450 that oxidatively decarbonylates aldehydes, was RNAi silenced specifically in oenocytes of both male and female D. melanogaster, resulting in marked inhibition of hydrocarbon production. The RNAi-silenced insects produced less than 10% of the hydrocarbon compared to control insects. Thus, the available evidence overwhelmingly supports oenocytes, whether associated with epidermal tissue or present in the peripheral fat body, as the site of cuticular hydrocarbon production. In some cases, even the shorter-chain hydrocarbon pheromones and pheromone precursors (see below) are produced in oenocytes. 

Typical biological compounds that are separated by HIC include, cytochrome P-450, enzymes, DNA polymerase, epidermal growth factor, glycoprotein hormones, human immunoglobulins, human recombinant DNA and canine pancreatic juice proteins. Many HIC techniques have been used for large scale purification of proteins. 

Pralavorio M, Lesca P, Rahmani R. 1998. Cytotoxic effects and induction of cytochromes P450 1A1/2 by insecticides, in hepatic or epidermal cells binding capability to the Ah receptor. Toxicol. Lett. 96/97 33-39... 

Enzyme inhibition is also a proposed mechanism of chaparral-induced hepatotoxicity (Sheikh et al., 1997). NDGA inhibits cytochrome P-450 activity in rat epidermal and hepatic microsomes (Agarwal, 1991). 

Agarwal R, Wang ZY, Bik DP, Mukhtar H. Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450 mediated monooxygenase activity in rat epidermal and hepatic microsomes. Drug Metab Dispos 1991 19 620-4. 

Li X, Kamenecka TM, Cameron MD (2010) Cytochrome P450-mediated bioactivation of the epidermal growth factor receptor inhibitor erlotinib to a reactive electrophile. Drug Metab Dispos 38 1238-1245... 

Du L, Hoffman SM, Keeney DS (2004) Epidermal CYP2 family cytochromes P450. Toxicol Appl Pharmacol 195 278-287... 

Slominski AT, Kim TK, Chen J, Nguyen MN, Li W, Yates CR, Sweatman T, Janjetovic Z, Tuckey RC (2012) Cytochrome P450s5 -dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes. Int J Biochem Cell Biol 44 2003-2018... 

Once a chemical reaches the viable epidermal layers, it may initiate a local effect, be absorbed into the circulation and produce an effect, or produce no local or systemic effects. The viable epidermis contains enzymes capable of metabolizing exogenous chemicals (Noonan and Wester 1983), including a substantial cytochrome P-450 system, esterases, mixed-function oxidases, and glucuronyltransferases. When the epidermal surface area is taken into account, then enzymatic activities of the epidermis can range from 80% to 240% of those in liver (Hotchkiss 1992). 

Imaging/Labeling Applications Amines/amino groups antibodies " bacteria blood vessels cells " chromosomes Culll) " dendrimers epidermal growth factor receptor (EGFR) folate histone deacetylases kinases nucleic acids/ nucleotides proteins " tumors Zn(ll) cytochrome c ... 

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