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1.
Cell Mol Biol (Noisy-le-grand) ; 69(8): 57-67, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37715413

ABSTRACT

Parkin is a member of the mitochondrial quality control system that plays a major role in mitophagy. Although the loss of function mutations in the Parkin gene has been associated with the Familial Parkinson's phenotype, research in recent years points out that Parkin's function is not limited to neurodegenerative diseases. Parkin's function impressing key cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, makes it an important player in the maintenance of cellular homeostasis. In this study, we investigated whether Parkin affects cell viability and ER stress responses under lipotoxic conditions in INS-1E cells. Our results may suggest that silencing Parkin may affect autophagy in addition to apoptosis.  We also showed that Parkin may have a protective effect against lipo-toxic effects in INS-1E cells. Consistent with previous studies, we observed that stress responses were different for high and low palmitic acid doses. The Parkin being inhibited under high-dose PA treatment and active under low-dose PA treatment indicate that regulation of stress responses is controlled by environmental conditions. Our preliminary findings may suggest that in low lipotoxic conditions, Parkin affects the ER stress response by modulating Chop activity and Ca2+ release from the ER to the cytoplasm.


Subject(s)
Insulin-Secreting Cells , Animals , Rats , Apoptosis , Autophagy , Cell Survival , Ubiquitin-Protein Ligases/genetics
2.
Jt Dis Relat Surg ; 32(2): 299-305, 2021.
Article in English | MEDLINE | ID: mdl-34145804

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the relationship between MMP13 rs3819089, ADAM12 rs3740199 and rs1871054, and ADAMTS14 rs4747096 genotypes in patients with radiologically diagnosed knee osteoarthritis (OA). PATIENTS AND METHODS: A total of 300 patients (68 males, 232 females; mean age: 61.6 years; range, 25 to 89 years) who were admitted to the orthopedics and traumatology clinic and diagnosed with knee OA according to the 2000 American College of Rheumatology (ACR) criteria between October 2018 and March 2019 were prospectively analyzed. Patients with Grades III-IV OA according to the Kellgren-Lawrence (K-L) grading system were included in the patient group (n=150) and those without radiological features of knee OA (K-L Grades I-II) were included in the control group (n=150) voluntarily. The presence of single nucleotide polymorphisms (SNPs) in the targeted genes in both groups was assessed by real-time polymerase chain reaction in the peripheral blood sample. RESULTS: The most common nucleotides in both the control and patient groups were CG for rs3740199 and CT for rs1871054 in the ADAM12 gene, and the most common nucleotides in alleles were GG for MMP13 rs3819089 and AA for ADAMTS14 rs4747096. No statistically significant relationship was detected between the gene polymorphisms and advanced OA. CONCLUSION: The study results suggest that ADAM12 rs3740199 and rs1871054, MMP13 rs3819089, and ADAMTS14 rs4747096 polymorphisms have no relationship with knee OA susceptibility in the Turkish population. However, as this is the first study to investigate the relationship between the SNPs of ADAM12, ADAMTS14, and MMP13 genes and the development of OA in the Turkish population, it would contribute to our understanding of the molecular bases of OA.


Subject(s)
ADAM12 Protein/genetics , ADAMTS Proteins/genetics , Matrix Metalloproteinase 13/genetics , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Prospective Studies , Radiography , Real-Time Polymerase Chain Reaction , Severity of Illness Index
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