Koriyama Yoshiki, Ogai Kazuhiro, Sugitani Kayo, Hisano Suguru, Kato Satoru
Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki, 513-8670, Suzuka, Japan.
Wellness Promotion Science Center, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 5-11-80 Kodatsuno, 920-0942, Kanazawa, Japan.
Adv Exp Med Biol. 2016;854:237-43. doi: 10.1007/978-3-319-17121-0_32.
Retinitis pigmentosa is a disease characterized by the loss of photoreceptor cells. The N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model is widely used to study the mechanism of these retinal degenerative disorders because of its selective photoreceptor cell death. As for the cell death mechanism of MNU, calcium-calpain activation and lipid peroxidation processes are involved in the initiation of this cell death. Although such molecular mechanisms of the MNU-induced cell death have been described, the total image of the cell death is still obscure. Heat shock protein 70 (HSP70) has been shown to function as a chaperon molecule to protect cells against environmental and physiological stresses. In this study, we investigated the effect of geranylgeranylacetone (GGA), an accylic polyisoprenoid, on MNU-induced photoreceptor cell loss. HSP70 induction by GGA was effective against MNU-induced photoreceptor cell loss as a result of its ability to prevent HSP70 degradation. The data indicate that GGA may help to suppress the onset and progression of retinitis pigmentosa.
视网膜色素变性是一种以光感受器细胞丧失为特征的疾病。N-甲基-N-亚硝基脲（MNU）诱导的视网膜变性模型因其选择性光感受器细胞死亡而被广泛用于研究这些视网膜退行性疾病的机制。至于MNU的细胞死亡机制，钙-钙蛋白酶激活和脂质过氧化过程参与了这种细胞死亡的起始。尽管已经描述了MNU诱导细胞死亡的此类分子机制，但细胞死亡的全貌仍然不清楚。热休克蛋白70（HSP70）已被证明作为一种伴侣分子发挥作用，以保护细胞免受环境和生理应激。在本研究中，我们研究了无环多异戊二烯香叶基香叶基丙酮（GGA）对MNU诱导的光感受器细胞丧失的影响。GGA诱导的HSP70因其防止HSP70降解的能力而对MNU诱导的光感受器细胞丧失有效。数据表明，GGA可能有助于抑制视网膜色素变性的发生和进展。
