Grazia Maugeri

Bio: Grazia Maugeri is an academic researcher from University of Catania. The author has contributed to research in topics: Medicine & Parkin. The author has an hindex of 20, co-authored 76 publications receiving 1054 citations.

Curcumin prevents high glucose damage in retinal pigment epithelial cells through ERK1/2-mediated activation of the Nrf2/HO-1 pathway.

Abstract: To study the effects of curcumin on human retinal pigment epithelial (RPE) cells exposed to high glucose (HG) insult, we performed in vitro studies on RPE cells cultured both in normal and HG conditions to assess the effects of curcumin on the cell viability, nuclear factor erythroid 2-related factor 2 (Nrf2) expression, HO-1 activity, and ERK1/2 expression. RPE cells exposed to HG insult were treated with curcumin. The cell viability, apoptosis, HO-1 activity, ERK, and Nrf2 expression were evaluated. The data indicated that treatment with curcumin caused a significant decrease in terms of apoptosis. Further, curcumin was able to induce HO-1 expression via Nrf2 activation and counteracts the damage elicited by HG. The present study demonstrated that curcumin provides protection against HG-induced damage in RPE cells through the activation of Nrf2/HO-1 signaling that involves the ERK pathway, suggesting that curcumin may have therapeutic value in the treatment of diabetic retinopathy.

PACAP Modulates Expression of Hypoxia-Inducible Factors in Streptozotocin-Induced Diabetic Rat Retina

Abstract: Retinal hypoxia has been related to the pathogenesis of diabetic retinopathy. This event is mediated by the hypoxia-inducible factors (HIFs), including HIF-1α, HIF-2α, and HIF-3α. Previously, we have demonstrated the protective role of pituitary adenylate cyclase-activating peptide (PACAP) in the early phase of diabetic retinopathy. In the present work, we investigated whether PACAP effect in hyperglycemic retina is mediated through modulation of HIFs’ expression. Diabetes was induced with a single injection of streptozotocin (STZ) in rats. After 1 week, a group of diabetic animals was treated with a single intravitreal injection of 100 μM PACAP or saline solution. Then, changes in HIFs’ expression levels were evaluated in the retina after 3 weeks of hyperglycemia. The expression of HIF-1α and HIF-2α was significantly (p < 0.001 vs control) increased in diabetic rats as compared to controls. Instead, their expression levels were significantly (p < 0.001 vs STZ) decreased after PACAP intraocular administration, as detected by Western blot analysis. Conversely, the expression of HIF-3α was significantly (p < 0.001 vs control) downregulated in retinas of STZ-injected rats and significantly (p < 0.001 vs control) increased after PACAP treatment. These data were supported by the immunohistochemical analysis. HIFs were localized either in inner and outer retinal layers. Diabetes interferes with their distribution, which is changed following intravitreal injection of PACAP. The present results suggest that the protective effect of the peptide in diabetic retina might be also mediated through modulation of HIFs’ expression.

Protective Effects of PACAP in Peripheral Organs.

Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects. PACAP is also expressed in peripheral organs but its peripheral protective effects have not been summarized so far. Therefore, the aim of the present paper is to review the existing literature regarding the cytoprotective effects of PACAP in non-neuronal cell types, peripheral tissues, and organs. Among others, PACAP has widespread expression in the digestive system, where it shows protective effects in various intestinal pathologies, such as duodenal ulcer, small bowel ischemia, and intestinal inflammation. PACAP is present in both the exocrine and endocrine pancreas as well as liver where it reduces inflammation and steatosis by interfering with hepatic pathology related to obesity. It is found in several exocrine glands and also in urinary organs, where, with its protective effects being mainly published regarding renal pathologies, PACAP is protective in numerous conditions. PACAP displays anti-inflammatory effects in upper and lower airways of the respiratory system. In the skin, it is involved in the development of inflammatory pathology such as psoriasis and also has anti-allergic effects in a model of contact dermatitis. In the non-neuronal part of the visual system, PACAP showed protective effects in pathological conditions of the cornea and retinal pigment epithelial cells. The positive role of PACAP has been demonstrated on the formation and healing processes of cartilage and bone where it also prevents osteoarthritis and rheumatoid arthritis development. The protective role of PACAP was also demonstrated in the cardiovascular system in different pathological processes including hyperglycaemia-induced endothelial dysfunction and age-related vascular changes. In the heart, PACAP protects against ischemia, oxidative stress, and cardiomyopathies. PACAP is also involved in the protection against the development of pre-senile systemic amyloidosis, which is presented in various peripheral organs in PACAP-deficient mice. The studies summarized here provide strong evidence for the cytoprotective effects of the peptide. The survival-promoting effects of PACAP depend on a number of factors which are also shortly discussed in the present review.

PACAP and VIP Inhibit HIF‐1α‐Mediated VEGF Expression in a Model of Diabetic Macular Edema

Abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert a protective role against retinal injuries, including diabetic macular edema (DME). The macular damage is induced by hyperglycemia, which damages vessels supplying blood to the retina and induces hypoxia. The microenvironmental changes stimulate the expression of hypoxia-inducible factors (HIFs), which promote the choroidal endothelial cell transmigration across the retinal pigmented epithelium (RPE) into neurosensory retina, where they proliferate into new vessels under stimulation of the vascular endothelial growth factor (VEGF). In the present study, we have investigated whether PACAP and VIP prevent retinal damage by modulating the expression of HIFs, VEGF, and its receptors. In accord to our hypothesis, we have shown that both peptides are able to significantly reduce HIF-1α and increase HIF-3α expression in ARPE-19 cells exposed to hyperglycemic/hypoxic insult. This effect is also related to a reduction of VEGF and its receptors expression. Moreover, both peptides also reduce the activation of p38 mitogen-activated protein kinase (MAPK), a pro-apoptotic signaling pathway, which is activated by VEGFR-1 and 2 receptors. In conclusion, our study has further elucidated the protective role performed by PACAP and VIP, against the harmful combined effect of hyperglycemia/hypoxia characterizing the DME microenvironment. J. Cell. Physiol. 232: 1209-1215, 2017. © 2016 Wiley Periodicals, Inc.

Mechanisms of mitophagy in cellular homeostasis, physiology and pathology.

Abstract: Mitophagy is an evolutionarily conserved cellular process to remove dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial number and preserving energy metabolism. In this Review, we survey recent advances towards elucidating the molecular mechanisms that mediate mitochondrial elimination and the signalling pathways that govern mitophagy. We consider the contributions of mitophagy in physiological and pathological contexts and discuss emerging findings, highlighting the potential value of mitophagy modulation in therapeutic intervention.

Changes in physical activity and sedentary behaviours from before to during the COVID-19 pandemic lockdown: a systematic review

Abstract: Objective In March 2020, several countries banned unnecessary outdoor activities during COVID-19, commonly called ‘lockdowns. These lockdowns have the potential to impact associated levels of physical activity and sedentary behaviour. Given the numerous health outcomes associated with physical activity and sedentary behaviour, the aim of this review was to summarise literature that investigated differences in physical activity and sedentary behaviour before vs during the COVID-19 lockdown. Design, data sources and eligibility criteria Electronic databases were searched from November 2019 to October 2020 using terms and synonyms relating to physical activity, sedentary behaviour and COVID-19. The coprimary outcomes were changes in physical activity and/or sedentary behaviour captured via device-based measures or self-report tools. Risk of bias was measured using the Newcastle-Ottawa Scale. Results Sixty six articles met the inclusion criteria and were included in the review (total n=86 981). Changes in physical activity were reported in 64 studies, with the majority of studies reporting decreases in physical activity and increases in sedentary behaviours during their respective lockdowns across several populations, including children and patients with a variety of medical conditions. Conclusion Given the numerous physical and mental benefits of increased physical activity and decreased sedentary behaviour, public health strategies should include the creation and implementation of interventions that promote safe physical activity and reduce sedentary behaviour should other lockdowns occur.