“
“The roles of sphingosine kinases SK1 and SK2 in ischemia-reperfusion injury have not been fully elucidated since studies have found beneficial effects of SK1 while others showed no role in this injury. To help resolve

this, we used SK1 or SK2 Verubecestat molecular weight knockout mice and confirmed that renal ischemia-reperfusion injury induced SK1, but not SK2, in the kidneys. Furthermore, knockout or pharmacological inhibition of SK1 increased injury after renal ischemia-reperfusion injury. In contrast, lack of SK2 conferred renal protection following injury. In addition, we used lentiviral gene delivery to selectively express enhanced green fluorescent protein (EGFP) or human SK1 coexpressed with EGFP (EGFP-huSK1) in the kidney. Mice with kidney-specific overexpression of EGFP-huSK1 had significantly improved renal function with lower plasma creatinine, renal necrosis, apoptosis, and inflammation. Moreover, EGFP-huSK1 overexpression in cultured human proximal tubule (HK-2) cells protected against peroxide-induced necrosis. Selective overexpression of EGFP-huSK1 led to increased HSP27 mRNA and protein expression in vivo and in vitro. Functional protection as well as induction selleck compound of HSP27 with EGFP-huSK1 overexpression in vivo was blocked with sphingosine-1-phosphate-1 receptor(1) (S1P(1)) antagonism. Thus, our findings suggest that SK1 is renoprotective by S1P(1) activation

and perhaps HSP27 induction. Kidney-specific expression of SK1 through lentiviral delivery may be a viable therapeutic option to attenuate renal ischemia-reperfusion injury.”
“Older adults show extensive variability in cognitive performance, including episodic memory. A portion of this variability could potentially

be explained by genetic factors. Recent literature shows that the neurotransmitter serotonin plays an important role in memory processes, as enhancements of brain serotonin have led to memory improvement. Sclareol Here, we have begun to explore genetic contributions to the performance and underlying brain activity associated with source memory monitoring. Using a source recognition memory task during fMRI scanning, this study offers evidence that older adults who carry a short allele (S-car) of the serotonin transporter linked polymorphic region (5-HTTLPR) in the SLC6A4 gene show specific deficits in source memory monitoring relative to older adults who are homozygous for the long allele (LL). These deficits are accompanied by less neural activity in regions of prefrontal cortex that have been shown to support accurate memory monitoring. Moreover, while the older adult LL group’s behavioral performance does not differ from younger adults, their brain activation reveals evidence of compensatory activation that likely supports their higher performance level.