Abstract
Dynamin-like protein I (DLP-1) is an important mitochondrial fission and fusion protein that is associated with apoptotic cell death in neurodegenerative diseases. In this study, we investigated DLP-1 expression in a focal cerebral ischemia animal model and glutamate-exposed hippocampal-derived cell line. Middle cerebral artery occlusion (MCAO) was surgically induced in adult male rats to induce focal cerebral ischemic injury. Brain tissues were collected 24 hours after the onset of MCAO. MCAO induces an increase in infarct volume and histopathological changes in the cerebral cortex. We identified a decrease in DLP-1 in the cerebral cortices of MCAO-injured animals using a proteomic approach and Western blot analysis. Moreover, glutamate treatment significantly decreased DLP-1 expression in a hippocampalderived cell line. The decrease in DLP-1 indicates mitochondrial dysfunction. Thus, these results suggest that neuronal cell injury induces a decrease in DLP-1 levels and consequently leads to neuronal cell death.
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Sims NR, Muyderman H. Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta 2010; 1802(1): 80–91.
Starkov AA, Chinopoulos C, Fiskum G. Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury. Cell Calcium 2004; 36(3-4): 257–264.
Goldenthal MJ, Marín-García J. Mitochondrial signaling pathways: a receiver/integrator organelle. Mol Cell Biochem 2004; 262(1-2): 1–16.
Abe K, Aoki M, Kawagoe J, Yoshida T, Hattori A, Kogure K, Itoyama Y. Ischemic delayed neuronal death. A mitochondrial hypothesis. Stroke 1995; 26(8): 1478–1489.
Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 2005; 47(3): 365–378.
Kageyama Y, Zhang Z, Sesaki H. Mitochondrial division: molecular machinery and physiological functions. Curr Opin Cell Biol 2011; 23(4): 427–434.
Reddy PH, Reddy TP, Manczak M, Calkins MJ, Shirendeb U, Mao P. Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Res Rev 2011; 67(1-2): 103–118.
Palmer CS, Osellame LD, Stojanovski D, Ryan MT. The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Cell Signal 2011; 23(10): 1534–1545.
Shirendeb U, Reddy AP, Manczak M, Calkins MJ, Mao P, Tagle DA, Reddy PH. Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington’s disease: implications for selective neuronal damage. Hum Mol Genet 2011; 20(7): 1438–1455.
Swerdlow RH. The neurodegenerative mitochondriopathies. J Alzheimers Dis 2009; 17(4): 737–751
Li H, Chen Y, Jones AF, Sanger RH, Collis LP, Flannery R, McNay EC, Yu T, Schwarzenbacher R, Bossy B, Bossy-Wetzel E, Bennett MV, Pypaert M, Hickman JA, Smith PJ, Hardwick JM, Jonas EA. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci U S A 2008; 105(6): 2169–2174.
Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Otera H, Nakanishi Y, Nonaka I, Goto Y, Taguchi N, Morinaga H, Maeda M, Takayanagi R, Yokota S, Mihara K. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat Cell Biol 2009; 11(8): 958–966.
Wakabayashi J, Zhang Z, Wakabayashi N, Tamura Y, Fukaya M, Kensler TW, Iijima M, Sesaki H. The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol 2009; 186(6): 805–816.
Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20(1): 84–91.
Sung JH, Cho EH, Min W, Kim MJ, Kim MO, Jung EJ, Koh PO. Identification of proteins regulated by estradiol in focal cerebral ischemic injury—a proteomics approach. Neurosci Lett 2010; 477(2): 66–71.
Koh PO. 17Beta-estradiol prevents the glutamate-induced decrease of Akt and its downstream targets in HT22 cells. J Vet Med Sci 2007; 69(3): 285–288.
Maher P, Davis JB. The role of monoamine metabolism in oxidative glutamate toxicity. J Neurosci 1996; 16(20): 6394–6401.
Tan S, Sagara Y, Liu Y, Maher P, Schubert D. The regulation of reactive oxygen species production during programmed cell death. J Cell Biol 1998; 141(6): 1423–1432.
Tiwari BS, Belenghi B, Levine A. Oxidative stress increased respiration and generation of reactive oxygen species, resulting in ATP depletion, opening of mitochondrial permeability transition, and programmed cell death. Plant Physiol 2002; 128(4): 1271–1281.
Pitts KR, Yoon Y, Krueger EW, McNiven MA. The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells. Mol Biol Cell 1999; 10(12): 4403–4417.
Smirnova E, Shurland DL, Ryazantsev SN, van der Bliek AM. A human dynamin-related protein controls the distribution of mitochondria. J Cell Biol 1998; 143(2): 351–358.
Nakahara I, Kikuchi H, Taki W, Nishi S, Kito M, Yonekawa Y, Goto Y, Ogata N. Changes in major phospholipids of mitochondria during postischemic reperfusion in rat brain. J Neurosurg 1992; 76(2): 244–250.
Siesjö BK, Elmér E, Janelidze S, Keep M, Kristián T, Ouyang YB, Uchino H. Role and mechanisms of secondary mitochondrial failure. Acta Neurochir Suppl 1999; 73: 7–13.
Hayashi T, Abe K. Ischemic neuronal cell death and organellae damage. Neurol Res 2004; 26(8): 827–834.
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Jang, AR., Koh, PO. Ischemic brain injury decreases dynamin-like protein 1 expression in a middle cerebral artery occlusion animal model and glutamate-exposed HT22 cells. Lab Anim Res 32, 194–199 (2016). https://doi.org/10.5625/lar.2016.32.4.194
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DOI: https://doi.org/10.5625/lar.2016.32.4.194