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Mathilde Malapel

Publications and source records attributed to Mathilde Malapel.

4 recordsLinked to original sources
PubMed2006

No evidence for an involvement of the p38 and JNK mitogen-activated protein in inflammatory bowel diseases.

Involvement of mitogen-activated protein (MAPK) in inflammatory bowel disease (IBD) remains enigmatic. We sought to evaluate the expression and activity of p38 and JNK MAPK in IBD and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis; and the effects of a p38 inhibitor, SB203580, in TNBS colitis. P38 and JNK were quantified in colonic mucosa of 28 IBD patients and 19 controls and in 77 TNBS or control mice treated or not with SB203580. Colitis severity was assessed by survival, macroscopic and microscopic scoring, and molecular markers. Expression and activity of p38 and JNK were similar in IBD patients and controls and not modified by inflammation. In mice, p38 and JNK expression or activity did not increase following the induction of colitis. SB203580 decreased the p38 activity but displayed no clinical nor biological therapeutic effect. In conclusion, these results minimize the role of p38 and JNK in inflammatory colitis and the interest of p38 as a therapeutic target in IBD.

Adult↗
PubMed2005

Hepatitis C virus infection down-regulates the expression of peroxisome proliferator-activated receptor alpha and carnitine palmitoyl acyl-CoA transferase 1A.

AIM: To elucidate the role of the peroxisome proliferator-activated receptor alpha (PPARalpha) and its target gene carnitine palmitoyl acyl-CoA transferase 1A (CPT1A) in the pathogenesis of hepatitis C virus (HCV) infection. METHODS: Liver samples were collected from the patients with chronic HCV infection and controls. HepG2 cells were transfected with vector pEF352neo carrying. Two independent clones (clone N3 and N4) stably expressing HCV core protein were analyzed. Total RNA was extracted from cells and liver tissues. PPARalpha and CPT1A mRNAs were quantified by real-time polymerase chain reaction (PCR) using SYBR Green Master. Total extracted proteins were separated by polyacrylamide gel electrophoresis, and electroblotted. Membranes were incubated with the anti-PPARalpha antibody, then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for PPARalpha. Protein bands were revealed by an enhanced chemiluminescence reaction for PPARalpha. For immunohistochemical staining of PPARalpha, sections were incubated with the primary goat polyclonal antibody directed against PPARalpha at room temperature. RESULTS: Real-time PCR indicated that the PPARalpha level and expression level of CPT1A gene in hepatitis C patients lowered significantly as compared with the controls (1.8+/-2.8 vs 13+/-3.4, P = 0.0002; 1.1+/-1.5 vs 7.4+/-1, P = 0.004). Western blot results showed that the level of PPARalpha protein in the livers of hepatitis C patients was lower than that in controls (2.3+/-0.3 vs 3.6+/-0.2, P = 0.009). The immunohistochemical staining results in chronic hepatitis C patients indicated a decrease in PPARalpha staining in hepatocytes compared with those in the control livers. The in vitro studies found that in the N3 and N4 colon stably expressing HCV core protein, the PPARalpha mRNA levels were significantly lower than that in the controls. CONCLUSION: The impaired intrahepatic PPARalpha expression is associated with the pathogenic mechanism in hepatic injury during chronic HCV infection. HCV infection reduced the expression of PPARalpha and CPT1A at the level of not only mRNAs but also proteins. PPARalpha plays an important role in the pathogenesis of chronic HCV infection, but the impaired function of this nuclear receptor in HCV infection needs further studies.

Carnitine O-Palmitoyltransferase↗
PubMed2005

Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection.

BACKGROUND AND AIMS: Liver inflammation, fibrosis, and dyslipidemia are common features in patients with chronic hepatitis C virus (HCV) infection. Because peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the liver and is involved in the regulation of lipid metabolism and inflammation, we sought to determine whether HCV infection may locally impair PPARalpha expression and activity. METHODS: PPARalpha expression was investigated in liver biopsy specimens of 86 untreated patients with HCV infection and controls, by using real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA). The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid. RESULTS: Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls. A mean decrease of 85% in PPARalpha mRNA expression paralleled with a lack of CPT1A mRNA induction also were observed in HCV core-expressing HepG2 cells compared with controls. CONCLUSIONS: HCV infection is related to altered expression and function of the anti-inflammatory nuclear receptor PPARalpha. These results identify hepatic PPARalpha as one mechanism underlying the pathogenesis of HCV infection, and as a new therapeutic target in traditional treatment of HCV-induced liver injury.

Biopsy↗