Kim Ji-Eun, Hyun Hye-Won, Min Su-Ji, Kang Tae-Cheon
Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym University Chuncheon, South Korea.
Front Cell Neurosci. 2017 Feb 22;11:47. doi: 10.3389/fncel.2017.00047. eCollection 2017.
Heat shock protein (HSP) 25 (murine/rodent 25 kDa, human 27 kDa) is one of the major astroglial HSP families, which has a potent anti-apoptotic factor contributing to a higher resistance of astrocytes to the stressful condition. However, impaired removals of HSP25 decrease astroglial viability. In the present study, we investigated whether HSP25 is involved in astroglial apoptosis or clasmatodendrosis (autophagic astroglial death) in the rat hippocampus induced by status epilepticus (SE). Following SE, HSP25 expression was transiently increased in astrocytes within the dentate gyrus (DG), while it was sustained in CA1 astrocytes until 4 weeks after SE. HSP25 knockdown exacerbated SE-induced apoptotic astroglial degeneration, but mitigated clasmatodendrosis accompanied by abrogation of endoplasmic reticulum (ER) stress without changed seizure susceptibility or severity. These findings suggest that sustained HSP25 induction itself may result in clasmatodendrosis via prolonged ER stress. To the best of our knowledge, the present study demonstrates for the first time the double-edge properties of HSP25 in astroglial death induced by SE.
热休克蛋白（HSP）25（小鼠/啮齿动物为25 kDa，人类为27 kDa）是主要的星形胶质细胞热休克蛋白家族之一，它是一种有效的抗凋亡因子，有助于星形胶质细胞对应激条件具有更高的抵抗力。然而，HSP25清除受损会降低星形胶质细胞的活力。在本研究中，我们调查了HSP25是否参与癫痫持续状态（SE）诱导的大鼠海马星形胶质细胞凋亡或树突自噬（自噬性星形胶质细胞死亡）。SE后，齿状回（DG）内星形胶质细胞中HSP25表达短暂增加，而CA1星形胶质细胞中HSP25表达持续至SE后4周。敲低HSP25会加剧SE诱导的凋亡性星形胶质细胞变性，但会减轻伴有内质网（ER）应激消除的树突自噬，且癫痫易感性或严重程度无变化。这些发现表明，持续诱导HSP25本身可能通过延长ER应激导致树突自噬。据我们所知，本研究首次证明了HSP25在SE诱导的星形胶质细胞死亡中的双重特性。
