Table 1.
Regulation of GS
| Factors | Net effect on GS |
Mechanism of Action | References |
|---|---|---|---|
| Gene mutations | |||
| R324C, R341C | ↓ | Disrupts synthesis of GS | (Haberle, et al. 2005) |
| Hormones | |||
| Glucocorticoids | ↑ | Induces gene via GRE and GS silencer element 5’ to GRE |
(Patejunas & Young 1990, Vardimon, et al . 1999, Vardimon, et al. 1988) |
| Estradiol/estrogen | ↑ | ↑ transcription of mRNA | (Blutstein, et al. 2006) |
| Insulin | ↓ | ↓ translation and activity of GS | (Khelil, et al. 1990) |
| Growth factors | |||
| BDNF | ↑ | Unknown | (Dai, et al. 2012) |
| Extracellular interactions | |||
| Excitatory synapses | ↑ | Glutamate or other factor | (Derouiche & Frotscher 1991) |
| Hyaluronan | ↓ | ↓ activity | (Moreno, et al. 2005) |
| Aggrecan | ↓ | ↓ differentiation of astrocytes | (Domowicz, et al. 2008) |
| E-cadherin (pancreas) | ↑ | ↑ Beta-catenin/Wnt-signaling | (Audard, et al. 2008) |
| Dickkopf-1 | ↓ | ↓ Beta-catenin/Wnt-signaling | (Busceti, et al. 2007) |
| Redox and beta amyloid | |||
| Oxidative stress | ↑ | GS oxidation → loss of function | (Butterfield, et al. 2006, Hensley, et al. 1995) |
| Nitrosative stress | ↓ | ↑NOS activity-> GS nitrosylation/nitration -> loss of function |
(Bidmon, et al. 2008, Kosenko, et al . 2003, Swamy, et al. 2011) |
| Fe3+ | ↓ | GS oxidation -> loss of function | (Fernandes, et al. 2011) |
| Beta amyloid | ↓ | GS oxidation -> loss of function | (Boyd-Kimball, et al. 2005) |
|
Inflammation/BBB disruption |
|||
| IL-1 beta + TNF-alpha | ↓ | ↑NO -> GS nitrosylation/ nitration -> loss of function; ↓, induction by glucocorticoids |
(Chao, et al. 1995, Huang & O’Banion 1998) |
| LPS | ↓ | ↑ IL-1 beta | (Letournel-Boulland, et al. 1994) |
| Thrombin | ↓ | ↓ differentiation of astrocytes | (Nelson & Siman 1990) |
|
Metabolites, cofactors metal ions and pH |
|||
| Glutamate | ↑ | Unknown | (Suarez, et al. 2002) |
| Ammonia | ↑ | Unknown | (Suarez, et al. 2002) |
| Increased pH | ↑ | Unknown | (Nissim 1999) |
| Decreased pH | ↓ | Unknown | (Nissim 1999) |
| Mn | ↓ | Unknown | (Deng, et al. 2012) |
| Exogenous compounds | |||
| Resveratrol | ↑ | ↑ GS activity | (dos Santos, et al. 2006) |
| Beta-L-ODAP | ↑ | ↑ GS activity via protein translation | (Miller, et al. 1993) |
| Methionine sulfoximine | ↓ | Irreversible inhibition of GS | (Ronzio & Meister 1968) |
| >40 other compounds, e.g. : –Tabtoxinine-beta-lactam –Alanosine |
↓ | V arious | Reviewed in (Eisenberg, et al. 2000) |
Abbreviations: GRE, glucocorticoid response element; NO, nitric oxide; NOS, nitric oxide synthetase; Beta-L-ODAP, beta-N-oxalyl-alpha, beta-diaminopropionic acid; Wnt, wingless/integrated