Alessandra Peres

Carnosic Acid Affords Mitochondrial Protection in Chlorpyrifos-Treated Sh-Sy5y Cells

Carnosic acid (CA; C20H28O4) is a phenolic diterpene found in rosemary (Rosmarinus officinalis L.) and exhibits protective properties, e.g., antioxidant, anti-inflammatory, antitumor, and antimicrobial activities. In this context, CA has been viewed as a neuroprotective agent due to its ability in rescuing neuronal cells from pro-oxidant and pro-apoptotic challenges. In the present work, we found that CA pretreatment at 1xa0µM for 12xa0h suppressed the mitochondria-related pro-oxidant and mitochondria-dependent pro-apoptotic effects of chlorpyrifos (CPF) in human neuroblastoma SH-SY5Y cells. CA prevented mitochondrial membrane potential disruption and decreased the levels of oxidative stress markers in mitochondrial membranes obtained from cells exposed to CPF. CA also inhibited cytochrome c release and activation of the caspases-9 and -3, as well as decreased DNA fragmentation, in CPF-treated cells. CA upregulated the content of glutathione (GSH) in mitochondria by a mechanism involving the activation of the phosphoinositide-3-kinase (PI3K)/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, since inhibition of PI3K/Akt or silencing of Nrf2 using siRNA strategy abolished the protection exerted by CA in SH-SY5Y cells. Therefore, CA protected mitochondria of SH-SY5Y cells through the activation of the PI3K/Akt/Nrf2 axis, causing upregulation of the mitochondrial GSH content and consequent antioxidant and anti-apoptotic effects.

Pinocembrin Provides Mitochondrial Protection by the Activation of the Erk1/2-Nrf2 Signaling Pathway in SH-SY5Y Neuroblastoma Cells Exposed to Paraquat

Pinocembrin (PB; 5,7-dihydroxyflavanone; C15H12O4) is a flavonoid found in propolis and exerts antioxidant, anti-inflammatory, and antimicrobial effects. Furthermore, PB has been studied as a neuroprotective agent. However, it remains to be understood whether and how PB would induce mitochondrial protection in mammalian cells. Therefore, we investigated here the mechanism involved in the protective effects elicited by PB in paraquat (PQ; 100xa0μM)-treated SH-SY5Y neuroblastoma cells. PB (25xa0μM) pretreatment (for 4xa0h) downregulated the levels of Bcl-2-associated X protein (Bax), blocked the release of cytochrome c to the cytosol, and inhibited the PQ-induced activation of caspase-9 and caspase-3. Besides, PB prevented mitochondrial dysfunction by suppressing the PQ-elicited inhibition of complexes I and V. Moreover, PB abrogated the loss of mitochondrial membrane potential (MMP) and the decline in ATP levels in the cells exposed to PQ. PB exerted antioxidant effects on mitochondria by decreasing the levels of redox impairment markers in mitochondrial membranes. Importantly, PB enhanced the levels of mitochondrial reduced glutathione (GSH). Upregulation of enzymes involved in the synthesis of GSH was seen in the cells exposed to PB. PB afforded mitochondrial protection by activating the extracellular signal-regulated kinase/nuclear factor erythroid 2-related factor 2 (Erk1/2-Nrf2) axis, since inhibition of Erk1/2 or silencing of Nrf2 abrogated these effects. Therefore, PB exerted mitochondrial and cellular protection by an Erk1/2-Nrf2-dependent mechanism.

Exercise-induced modulation of histone H4 acetylation status and cytokines levels in patients with schizophrenia

The present study aimed to investigate the short and long-term effects of a concurrent exercise protocol on global histone H4 acetylation levels and inflammatory markers (interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma (IFN-γ) and cortisol) in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC) and in peripheral blood of patients with schizophrenia (SZ), as well the intervention impact on anthropometric characteristics. Seventeen individuals were submitted to the intervention three times a week and blood samples were collected pre, 30, 60 and 90days after the intervention started. A remarkable reduction on body mass index and body mass were observed following intervention. The protocol also induced a histone H4 hypoacetylation status in PBMC all times evaluated when compared to the pre intervention period. Although the IL-4 and cortisol levels were not altered in response to the intervention, a reduction in IL-6 production during the 60 and 90days compared to the pre intervention period was observed. Finally, diminished IFN-γ production was found in the 90days period compared to the pre intervention and 30days after periods. In addition, systemic IL-6 levels were lower at 60 and 90days compared to the pre intervention. The concurrent exercise protocol was able to improve anthropometric characteristics in patients with SZ, engaging the modulation of cytokine and histone H4 acetylation levels.

Chronic purple grape juice consumption induces age-dependent changes on cognitive function in elderly women

Objective: To verify the chronic consumption of grape juice effects on weight, body mass index (BMI), cognitive function and the peripheral levels of global histone H4 acetylation, BDNF and inflammatory markers in elderly women according to age. Methods: This is a quasi-experimental study. The blood samples were collected before and after 30 days of grape juice supplementation (400 ml/daily) in women aged > 70 and < 70 years old. Weight, BMI and cognitive function, were measured before and after supplementation. Results: Grape juice consumption promoted a reduction on weight and BMI. This consumption also contributed to improve a cognitive function. These effects were more pronounced in the >70 years group. A tendency towards increased BDNF levels was observed in the >70 years group after intervention. Inflammatory markers and global histone H4 levels did not change. Conclusion: The chronic grape juice consumption is an interesting choice to promote health benefits in elderly women, which seem to act in an age-dependent manner. Correspondence to: Viviane Rostirola Elsner , Postgraduate Program in Biosciences and Rehabilitation of the Methodist University Center of IPA. Rua Coronel Joaquim Pedro Salgado, 80 Rio Branco, Porto Alegre RS, CEP 90420060; Telephone / fax number: +55 51 3316 1100; E-mail: vivielsner.fisiologia@gmail.com

The Running Practice Modulates Inflammatory Markers and not Alters Global DNA Methylation in Elderly Men

Objectives: The current study aimed to evaluate 1) the impact of the regular running practice 2) as well the acute effect of running race on inflammatory markers and DNA methylation status in peripheral blood of health elderly men. Methods: Fifteen male volunteers aged 60 years and older were recruited. They were allocated in two groups: runners (RUN, n=8) and sedentary (SED, n=7), considering if they were sedentary or amateur street runners. All participants, SED and RUN groups, were submitted to a basal blood collection. After 5 days, two blood samples were collected in the RUN group: 30 min before and immediately after a 5-10km outdoor running performance.The blood samples (15mL) were collected for the epigenetic and inflammatory measurements, which were done using specific kits, according to the manufacturer’s instructions. Results: FIn the basal period, no significant differences were observed on DNA global methylation status between the SED and RUN groups. However, the SED group showed increased IL-4 and IL-6 levels when compared to the RUN individuals (p= 0,040 and 0,035, respectively). The IL-6 and IL-4 levels were significantly higher in the EXE group after the running performance compared to the before running period (p=0,004 and 0,013 respectively), while DNA methylation status remained unaltered. Conclusion: Our data suggest that DNA methylation status might not be consider a potential biomarker related to the healthy elderly runners phenotype. Furthermore, the inflammatory response may indicate a possible regulatory effect provided by the endurance exercise in the elderly group because IL-4 and IL-6 are synergic cytokines directing an immune response.