Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons

Metformin is a widely prescribed drug used to treat type-2 diabetes, although recent studies show it has wide ranging effects to treat other diseases. Animal and retrospective human studies indicate that Metformin treatment is neuroprotective in Parkinson’s Disease (PD), although the neuroprotective mechanism is unknown, numerous studies suggest the beneficial effects on glucose homeostasis may be through AMPK activation. In this study we tested whether or not AMPK activation in dopamine neurons was required for the neuroprotective effects of Metformin in PD. We generated transgenic mice in which AMPK activity in dopamine neurons was ablated by removing AMPK beta 1 and beta 2 subunits from dopamine transporter expressing neurons. These AMPK WT and KO mice were then chronically exposed to Metformin in the drinking water then exposed to MPTP, the mouse model of PD. Chronic Metformin treatment significantly attenuated the MPTP-induced loss of Tyrosine Hydroxylase (TH) neuronal number and volume and TH protein concentration in the nigrostriatal pathway. Additionally, Metformin treatment prevented the MPTP-induced elevation of the DOPAC:DA ratio regardless of genotype. Metformin also prevented MPTP induced gliosis in the Substantia Nigra. These neuroprotective actions were independent of genotype and occurred in both AMPK WT and AMPK KO mice. Overall, our studies suggest that Metformin’s neuroprotective effects are not due to AMPK activation in dopaminergic neurons and that more research is required to determine how metformin acts to restrict the development of PD

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan

Etapy mikrobiologicznego rozkladu folii polietylenowej modyfikowanej syntetycznym poliestrem przez wybrane bakterie glebowe

Celem badań było określenie podatności folii polietylenowej modyfikowanej poliestrem Bionolle®, na biodegradację przez wybrane bakterie glebowe. Oznaczano ubytek masy polimerów, obserwowano powierzchnię próbek w skaningowym mikroskopie elektronowym oraz analizowano folie w podczerwieni Stwierdzono różne mechanizmy degradacyjne folii u zastosowanych szczepów bakterii. Bacillus cereus, posiadający wewnątrzkomórkową depolimerazę PHB, degradował tworzywo po jego wcześniejszej hydrolizie abiotycznej do niskocząsteczkowych fragmentów. Inicjacja degradacji polimerów przez zewnątrzkomórkową depolimerazę Pseudomonas stutzeri nie wymagała wcześniejszego rozkładu wielkocząsteczkowego substratu. Folia polietylenowa, modyfikowana syntetycznym poliestrem Bionolle®, podlegała przyspieszonej bakteryjnej biodegradacji w porównaniu do polietylenu niemodyfikowanego.The biodegradability of polyethylene modified with Bionolle® polyester with the use of Bacillus cereus and Pseudomonas stutzeri bacteria, was studied. Degradation of the polymeric films was monitored by weight loss, scanning electron microscopy (SEM) and FTIR-spectroscopy. Different mechanisms of biodegradation were observed. The Bacillus cereus strain, which is well known as synthesizing intracellular PHA depolymerase, decomposed films after their previous abiotic hydrolysis. The rate of polymer biodegradation by P. stutzeri was higher than by B. cereus. It was concluded that the excretion of extracellular enzymes produced by P. stutzeri made easier utilization of decomposed compounds