TIMP

Tissue inhibitor of metalloproteins (TIMP, from human blood plasma), Mr -30,000. 

Purified by a [anti-human amniotic fluid-TIMP]-Sepharose immuno-affinity column eluted with 50mM glycine/HCl pH 3.0 buffer that is 0.5M in NaCl then by gel film [Cawston et al. Biochem J 238 677 1986]. 

The enzymatic activity of these potentially harmful enzymes is tightly controlled. Once transcribed into protein, MMPs are expressed as inactive zymogens and require distinct activation processes to convert them into active enzymes. After secretion, MMP-activity is regulated by the noncovalent binding of tissue inhibitors of metalloproteinases ( TIMPs) as shown in Fig. 2 for MMP-2 and TIMP-2. Four TIMPs have been identified so far TIMP-1, TIMP-2, TIMP-3, and TIMP-4. All known MMPs can be inhibited by at least one of the four known TIMPs. Nevertheless, individual differences with regard to bond strength and thus the magnitude of inhibition of a particular MMP do exist. 

Matrix Metalloproteinases. Figure 2 ProMMP-2-TIMP-2 structure (adopted from [4]). TIMP-2 cartoon and transparent surface structure is shown in blue, MMP-2 in red. The C-terminal ends of both molecules are marked as spheres. 

Hemmann S, Graf J, Roderfeld M et al (2007) Expression of MMPs and TIMPs in liver fibrosis—a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 46 955-975... 

The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors TIMP-1, TIMP-2, TIMP-3, and TIMP-4. Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in the latent form. 

Besides aromatic hydrocarbons such as pyrene (above), benzanthracene (Becker et al., 1977a), benzoin derivatives (Baumann et al., 1982), aromatic and heteroaromatic ketones (Fomin et al., 1980 Baumann et al., 1985), azo dyes (Timpe et al., 1982), methylene blue (Becker et al., 1986 a Becker and Kohrs, 1990), acridine yellow... 

Gelman BB, Wolf DA, Rodriguez-Wolf M et al (1997) Mononuclear phagocyte hydrolytic enzyme activity associated with cerebral HIV-1 infection. Am J Pathol 151 1437-1446 Giraudon P, Buart S, Bernard A et al (1997) Cytokines secreted by gUal cells infected with HTLV-I modulate the expression of matrix metalloproteinases (MMPs) and their natural inhibitor (TIMPs) possible involvement in neurodegenerative processes. Mol Psychiatry 2(107-10) 84... 

TIMP-1, TIMP-2 Tissue inhibitors of metalloproteinases 1 and 2 Ha Thymus leukaemia antigen TLC TTiin-layer chromatt raphy TLCK Tosyl-lysyl-CHiCl TLP Tumour-like proliferation Tm T memory... 

Eichner SF, Lloyd KB, Timpe EM. Comparing therapies for postmenopausal osteoporosis prevention and treatment. Ann Pharmacother 2003 37 711-724. 

It has been demonstrated in other cell types that lutein can inhibit expression of MMPs and/ or activity (Philips et al., 2007). For example, in dermal fibroblasts lutein inhibits expression of MMP-1 and decreases levels of MMP-2 protein (Philips et al., 2007). In melanoma cells, lutein inhibits MMP-1 expression while stimulating TIMP-2 (Philips et al., 2007). Moreover it has been shown that lutein inhibits elastin expression in fibroblasts subjected to oxidative stress by exposure to ultraviolet light (Philips et al., 2007). These results clearly indicate that lutein can play an important role in remodeling of the extracellular matrix. 

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