WWL 70

WWL 70 is a potent inhibitor of α/β-hydrolase domain 6 (ABHD6) with IC50 value of 70 nM [1].

WWL 70 is an O-aryl group-modified derivative of carbamate 18 which is a lead inhibitor of ABHD6 screened out by a functional proteomic strategy. WWL 70 is about 5-fold more potent than carbamate 18. The improved potency makes no difference in selectivity of WWL 70 and carbamate 18 as measured by competitive ABPP with brain membrane proteome. WWL 70 was selective against ABHD6 over other 27 SH activities except for ABHD10 which showed a significant reduction in activity in WWL 70-treated proteomes. However, WWL 70 had no effect on recombinant ABHD10 at concentration of 100 μM, suggesting that ABHD10 was not a real target [1].

References:
[1] Li W, Blankman J L, Cravatt B F. A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. Journal of the American Chemical Society, 2007, 129(31): 9594-9595.

Comparison of Recombinant Proteins of Kinesin 39, Heat Shock Protein 70, Heat Shock Protein 83, and Glycoprotein 63 for Antibody Detection of Leishmania martiniquensis Infection.[Pubmed:28370779]

J Eukaryot Microbiol. 2017 Nov;64(6):820-828.

Leishmania martiniquensis, a zoonotic hemoflagellate, is a causative agent of cutaneous (CL) and visceral leishmaniasis (VL) among humans and animals. This organism, first reported in Martinique Island, now has become an emerging infectious agent in Thailand. Symptomatic cases of L. martiniquensis infection among humans have continuously increased. In the meantime, asymptomatic infection of this novel species has seriously created national public health awareness and concern to prevent and control disease transmission. The unsuccessful serological test using the commercial rK39 dipstick based on antigen from Leishmania donovani to detect the antibodies against VL among infected Thai patients has encouraged us to further explore a new sensitive and specific antigenic epitope. In this study, we determined the sequences and expressed recombinant proteins of kinesin 39 (k39), heat shock protein 70 (hsp70), heat shock protein 83 (hsp83), and glycoprotein 63 (gp63) of L. martiniquensis to evaluate the diagnostic efficiency to detect antibodies against L. martiniquensis in patient sera. The preliminary results from western blot analysis have suggested that K39 is the most sensitive recombinant protein to detect L. martiniquensis. Moreover, this recombinant protein reacts with antibodies against L. donovani and Leishmania infantum, making it a promising antigen for further development of a universal rapid diagnostic tool for VL.

Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2.[Pubmed:28367089]

Int J Med Sci. 2017 Feb 25;14(3):284-293.

Tumor necrosis factor alpha (TNFalpha) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFalpha on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFalpha stimulus. We observed that HepG2 cell revealed a higher resistance to TNFalpha-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFalpha, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFalpha/control ratio>2.0 or <0.5) by immunoblotting using specific antibodies. We also analyzed the differential expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFalpha might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFalpha. Collectively, these findings indicate that TNFalpha alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.

Resistance training is linked to heightened positive motivational state and lower negative affect among healthy women aged 65-70.[Pubmed:28375777]

J Women Aging. 2018 Sep-Oct;30(5):366-381.

Resistance training (RT) improves overall health, but the psychological effects of RT in healthy old adults have not been tested. The aim of this study was to investigate a sample of 65-70-year-old healthy and physically active women to assess their sense of coherence, health-related quality of life, hope, and affect, before and after taking part in a 24-week RT intervention (N = 14), compared to controls (N = 18). Findings showed a significant increase in hope (p = 0.013) and a significant decrease in negative affect (p = 0.002). Starting RT after age 65 does not appear to negatively impact on women's psychological health but seems to be associated with important psychological health benefits.

A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol.[Pubmed:18096503]

Chem Biol. 2007 Dec;14(12):1347-56.

Endogenous ligands for cannabinoid receptors ("endocannabinoids") include the lipid transmitters anandamide and 2-arachidonoylglycerol (2-AG). Endocannabinoids modulate a diverse set of physiological processes and are tightly regulated by enzymatic biosynthesis and degradation. Termination of anandamide signaling by fatty acid amide hydrolase (FAAH) is well characterized, but less is known about the inactivation of 2-AG, which can be hydrolyzed by multiple enzymes in vitro, including FAAH and monoacylglycerol lipase (MAGL). Here, we have taken a functional proteomic approach to comprehensively map 2-AG hydrolases in the mouse brain. Our data reveal that approximately 85% of brain 2-AG hydrolase activity can be ascribed to MAGL, and that the remaining 15% is mostly catalyzed by two uncharacterized enzymes, ABHD6 and ABHD12. Interestingly, MAGL, ABHD6, and ABHD12 display distinct subcellular distributions, suggesting that they may control different pools of 2-AG in the nervous system.