Mohammad Reza Dayer, Nooshin Azari, Nematollah Razmi, Mohammad Saeid Dayer,
Volume 17, Issue 7 (10-2014)
Abstract
Background: Prion diseases are neurodegenerative disorders which ultimately results in the death of their victims. They are caused by structural transformation of cellular prion (PrPC) to its &beta-rich and anomalous isoform (PrPSc) and the accumulation of amyloid fibrillar deposits in the central nervous system. The precise mechanism underling this conversion is yet to be well understood. This study aimed to investigate the effect of non physiological temperatures on the misfolding mechanism of the human prion protein.
Materials and Methods: The crystal structure of human prion protein (90-231), (PDB code: 2Lej) in pdb format was used as a starting structure in this study. Three model structures of this coordinate structure were used separately to simulate PrPC at 27 , 37 and 47 . Molecular dynamic simulations were then performed using double-precision MPI version of GROMACS 4.5.5 for 10 ns and the results were analyzed using SPSS software, SPDBV and VebLab programs.
Results: The change of temperature from 37 to 27 or 47 induced significant structural changes to PrPC. These tempratures caused PrPC to attain a more folded and less flexible tertiary structure compared to its native structure at 37 . They, also, reduce protein-solvent hydrogen bonds and therefore increasing access of hydrophobic solvent to PrPC which may be behind the lower water solubility of PrPC and its increased resistance to proteolytic degradations.
Conclusion: This study shows that changes of temperatures accelerate structural changes of PrPC and reduce its solubility while rendering it vulnerable to transition into PrPSc.
Roya Fatemi Nejad, Mohammad Reza Dayer, Mehran Dorostghoal, Mohammad Reza Parishani,
Volume 28, Issue 4 (10-2025)
Abstract
Introduction: Botulinum neurotoxin protein (Botox) is widely used for cosmetic purposes to reduce facial wrinkles without regard to its side effects. The present study was conducted to investigate the effects of Botox on blood biochemical factors and the kidney tissue structure of female rats.
Methods: In this study, 28 adult female Wistar rats were selected and randomly divided into four groups (n = 7). The first three groups received intraperitoneal injections of Botox (in the lower third of the abdomen, one centimeter below and to the left of the navel) at doses of 4, 6, and 8 units, respectively, while the fourth group (the control group) received a saline injection. Then the animals were kept in the animal house for three months with full access to food and water at a temperature of 22°C and a 12-hour light-dark cycle. Following a 24-hour fasting period at the end of the study, blood samples were collected via cardiac puncture under ether anaesthesia. Then, the animals were euthanized without pain, and their kidney tissue samples were extracted for histological examination.
Results: Biochemical results indicated a significant increase in serum creatinine levels following injection with 6 and 8 units of Botox, indicating renal impairment. Although the increase in the amount of serum uric acid levels compared to the control group did not reach statistical significance at the 95% confidence level (P < 0.05), it showed significance at the 94% level (p < 0.06), suggesting primary renal damage. Histopathological examination demonstrated that intraperitoneal injection of 8 units of Botox induced scattered and limited structural alterations in renal tissue, including vacuolar degeneration of tubular epithelial cells.
Conclusions: The results of this research show that the long-term and repeated use of Botox may cause significant renal damage in addition to local lesions and threaten a person's life.
