Cell apoptosis and proliferation in rat brains after intracerebral hemorrhage: role of Wnt/b-catenin signaling pathway

To investigate the role of Wnt/b-catenin signaling pathway in cell apoptosis and proliferation in intracerebral hemorrhage (ICH) in rats. Materials and methods: The ICH rats were established by stereotaxic infusion of 50 µL autologous arterial blood into the right striatum. Pathological characteristics of brain tissue was assessed by hematoxylin and eosin and TUNEL staining, and the expressions of proliferating cell nuclear antigen (PCNA) and Wnt3a/b-catenin/cyclin D1 were investigated by immunohistochemistry or reverse-transcription polymerase chain reaction. Results: The number of apoptotic cells and PCNA-positive cells kept increasing from the day following the ICH induction and reached a peak on the 3rd and 14th days, respectively. Some of the PCNA-positive cells could coexpress neurofilament protein-200 or glial fibrillary acidic protein. Wnt3a, b-catenin, cyclin D1, and PCNA mRNAs reached maximal expression levels on the 3rd, 7th, 7th, and 14th days, respectively. Moreover, the number of apoptotic cells was significantly positively correlated with the expressions of Wnt3a and b-catenin mRNAs, and negatively correlated with the number of PCNA-positive cells. Conclusion: Our results suggest that the Wnt/b-catenin signaling pathway is associated with cell apoptosis and expression of PCNA in the ICH rat brain and regulates the balance between cell apoptosis and proliferation.

Cell apoptosis and proliferation in rat brains after intracerebral hemorrhage: role of Wnt/b-catenin signaling pathway

To investigate the role of Wnt/b-catenin signaling pathway in cell apoptosis and proliferation in intracerebral hemorrhage (ICH) in rats. Materials and methods: The ICH rats were established by stereotaxic infusion of 50 µL autologous arterial blood into the right striatum. Pathological characteristics of brain tissue was assessed by hematoxylin and eosin and TUNEL staining, and the expressions of proliferating cell nuclear antigen (PCNA) and Wnt3a/b-catenin/cyclin D1 were investigated by immunohistochemistry or reverse-transcription polymerase chain reaction. Results: The number of apoptotic cells and PCNA-positive cells kept increasing from the day following the ICH induction and reached a peak on the 3rd and 14th days, respectively. Some of the PCNA-positive cells could coexpress neurofilament protein-200 or glial fibrillary acidic protein. Wnt3a, b-catenin, cyclin D1, and PCNA mRNAs reached maximal expression levels on the 3rd, 7th, 7th, and 14th days, respectively. Moreover, the number of apoptotic cells was significantly positively correlated with the expressions of Wnt3a and b-catenin mRNAs, and negatively correlated with the number of PCNA-positive cells. Conclusion: Our results suggest that the Wnt/b-catenin signaling pathway is associated with cell apoptosis and expression of PCNA in the ICH rat brain and regulates the balance between cell apoptosis and proliferation.

___

  • Zhou F, Chen G, Zhang J. Edaravone reduces brain oedema and attenuates cell death after intracerebral haemorrhage in mice. Brain Inj 2009; 23: 353–357.
  • Davidson KC, Adams AM, Goodson JM, McDonald CE, Potter
  • JC, Berndt JD, Biechele TL, Taylor RJ, Moon RT. Wnt/β-catenin
  • signaling promotes differentiation, not self-renewal, of human
  • embryonic stem cells and is repressed by Oct4. Proc Natl Acad
  • Sci U S A 2012; 109: 4485–4490.
  • Yang CX, Zhou L, Deng L, Gao XQ. Do neural precursor cells exist in a distal neurogenic region following cerebral hemorrhage? Neural Regen Res 2010; 5: 325–330. 9. Garcia JH, Liu KF, Ye ZR, Gutierrez JA. Incomplete infarct and delayed neuronal death after transient middle cerebral artery occlusion in rats. Stroke 1997; 28: 2303–2309.
  • Yang C, Zhou L, Gao X, Chen B, Tu J, Sun H, Liu X, He J, Liu J, Yuan Q. Neuroprotective effects of bone marrow stem cells overexpressing glial cell line-derived neurotrophic factor on rats with intracerebral hemorrhage and neurons exposed to hypoxia/reoxygenation. Neurosurgery 2011; 68: 691–704.
  • Miao X, Liu X, Yue Q, Qiu N, Huang W, Wang J, Xu Y, Zhang Y, Yang J, Chen X. Deferoxamine suppresses microglia activation and protects against secondary neural injury after intracerebral hemorrhage in rats. Nan Fang Yi Ke Da Xue Xue Bao 2012; 32: 970–975 (article in Chinese with abstract in English).
  • Kikuchi A, Yamamoto H, Sato A, Matsumoto S. New insights into the mechanism of Wnt signaling pathway activation. Int Rev Cell Mol Biol 2011; 291: 21–71.
  • Heller RS, Klein T, Ling Z, Heimberg H, Katoh M, Madsen OD, Serup P. Expression of Wnt, Frizzled, sFRP, and DKK genes in adult human pancreas. Gene Expr 2003; 11: 141–147.
  • Li W, Tong H, Huang X, Wang W, Wu H, Lin S. High levels of β-catenin promote IFNγ-induced apoptosis in hepatocellular carcinoma cells. Oncol Lett 2012; 4: 1092–1096.
  • Biechele TL, Kulikauskas RM, Toroni RA, Lucero OM, Swift RD, James RG, Robin NC, Dawson DW, Moon RT, Chien AJ. Wnt/β-catenin signaling and AXIN1 regulate apoptosis triggered by inhibition of the mutant kinase BRAFV600E in human melanoma. Sci Signal 2012; 5, ra3.
  • Kim K, Pang KM, Evans M, Hay ED. Overexpression of beta- catenin induces apoptosis independent of its transactivation function with LEF-1 or the involvement of major G1 cell cycle regulators. Mol Biol Cell 2000; 11: 3509–3523.
  • Qureshi AI, Suri MF, Ostrow PT, Kim SH, Ali Z, Shatla AA, Guterman LR, Hopkins LN. Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery 2003; 52: 1041– 1048.
  • Zhang XQ, Zhang ZM, Yin XL, Zhang K, Cai H, Ling F. Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage: tracking the expression and progress of cell apoptosis of prehematomal brain tissues. Chin Med J (Engl) 2010; 123: 1246–1250.
  • Meirmanov S, Nakashima M, Kondo H, Matsufuji R, Takamura N, Ishigaki K, Ito M, Prouglo Y, Yamashita S, Sekine I. Correlation of cytoplasmic beta-catenin and cyclin D1 overexpression during thyroid carcinogenesis around Semipalatinsk nuclear test site. Thyroid 2003; 13: 537–545.
  • Kumar DU, Devaraj H. Expression of Wnt 3a, β-catenin, cyclin D1 and PCNA in mouse dentate gyrus subgranular zone (SGZ): a possible role of Wnt pathway in SGZ neural stem cell proliferation. Folia Biol (Praha) 2012; 58: 115–120.
  • Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R, Ben-Ze’ev A. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci U S A 1999; 96: 5522–5527.
  • Macas J, Nern C, Plate KH, Momma S. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J Neurosci 2006; 26: 13114–13119.
  • Moon SU, Kim J, Bokara KK, Kim JY, Khang D, Webster TJ, Lee JE. Carbon nanotubes impregnated with subventricular zone neural progenitor cells promotes recovery from stroke. Int J Nanomedicine 2012; 7: 2751–2765.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Relationship between placental localisation, birth weight, umbilical Doppler parameters, and foetal sex

Müzeyyen Duran ERDOLU, Aydın KÖŞÜŞ, Nermin KÖŞÜŞ, Gülçin DİLMEN, Hasan KAFALI

Evaluation of scleral-fixated intraocular lens position anomalies by anterior segment optical coherence tomography

Nihat POLAT, Kemalettin Kazım DEVRANOĞLU, Mehmet Akif ÖZDAMAR, Ceyhun ARICI

The increase of mean platelet volume in patients with Alzheimer disease

Emine Rabia KOÇ, Ertuğrul UZAR, Yasemin ÇIRAK, Yasemin Parlak DEMİR, Atilla İLHAN

Association analyses of oxidative stress, aerobic capacity, daily physical activity, and body composition parameters in patients with mild to moderate COPD

Abdurrahman GENÇ, Kağan ÜÇOK, Ümit ŞENER, Tülay KOYUNCU, Olcay AKAR, Sefa ÇELİK, Mehmet ÜNLÜ

Behavioural and neurobiological consequences of 2 different chronic stressors in rats

Refia Aslıhan DÖNMEZ, Fatma Duygu KAYA, Okşan DERİNÖZ, Ömer Hakan EMMEZ

A new knot-supporting instrument and knot technique for laparoscopic surgery

Hasan BÖREKCİ, Elif BÖREKCİ, Hakan AK, Kürşad ZENGİN, Tugay ATALAY, Serhat TANIK

Is the combined use of insulin resistance indices, including adipokines, more reliable in metabolic syndrome?

Birgül KURAL, Orhan DEĞER, Cihangir EREM, Fulya BALABAN YÜCESAN

Vitamin C as an antioxidant: evaluation of its role on pulmonary contusion experimental model

Rana SIRMALI, Zeynep GİNİŞ, Mehmet SIRMALI, Okan SOLAK, Bengü ŞELİMAN, Yetkin AĞAÇKIRAN, Namık DELİBAŞ

Detection the frequency of PER-1 type extended-spectrum ß-lactamase-producing Acinetobacter baumannii clinical isolates in Turkey: a multicenter study

Detection Of The Frequency Of Per- Type STUDY

Investigation of linezolid resistance in Staphylococcus epidermidis: first reported linezolid resistant coagulase negative staphylococcus in Turkey

Barış YALÇIN, Mehmet Burak SELEK, Bayhan BEKTÖRE, Tuğrul HOŞBUL, Mustafa ÖZYURT