RESUMEN
AT-HOOK MOTIF NUCLEAR LOCALIZED (AHL) proteins occur in all sequenced plant species. They bind to the AT-rich DNA sequences in chromosomes and regulate gene transcription related to diverse biological processes. However, the molecular mechanism underlying how AHL proteins regulate gene transcription is poorly understood. In this research, we used root hair production as a readout to study the function of two Arabidopsis AHL proteins, AHL17, and its closest homolog AHL28. Overexpression of AHL17 or AHL28 greatly enhanced root hair production by increasing the transcription of an array of genes downstream of RHD6. RHD6 is a key transcription factor that regulates root hair development. Mutation of RHD6 completely suppressed the overproduction of root hairs by blocking the transcription of AHL17-activated genes. The overexpression of AHL17 or AHL28, however, neither affected the transcription of RHD6 nor the accumulation of RHD6 protein. These two AHL proteins also did not directly interact with RHD6. Furthermore, we found that three members of the Heat Shock Protein70 family, which have been annotated as the subunits of the plant Mediator complex, could form a complex with both AHL17 and RHD6. Our research might reveal a previously unrecognized mechanism of how AHL proteins regulate gene transcription.
RESUMEN
BACKGROUND: Intracerebral hemorrhage (ICH) is a common neurological emergency with higher mortality and disability rate than cerebral ischemia. Although diverse therapeutic interventions have been explored for potential neuroprotection from ICH, no effective drugs until now are available for improvement of survival rate or the life quality of survivors after ICH. Just like cerebral ischemia, inflammatory mechanism is highly thought to play a vital role in hemorrhagic brain injury. Ligustilide (LIG) has potent anti-inflammatory effects, which were shown to be closely related to its neuroprotective effects against ischemic brain injury. Senkyunolide H (SH) and senkyunolide I (SI) are natural degradation products of LIG, which contain the mother nucleus structure of LIG as that of phthalide. However, no reports have been retrieved about the neuroprotective effects of the three phthalide compounds on ICH, especially from the perspectives of inflammatory pathways. Accordingly, this study investigated the neuroprotective potentials and mechanisms of LIG, SH and SI on experimental ICH in mice. METHODS: ICH was induced in adult male CD-1 mice by intracerebral injection of autologous blood. LIG, SH and SI, respectively, was administrated after ICH induction. Neurological deficits, brain edema, injury volume, the number of surviving/dying neurons and inflammatory gene expression were evaluated at 3â¯days after ICH. RESULTS: Neurological deficits, brain edema, neuronal injury, microglia and astrocytes activation as well as peripheral immune cells infiltration were all significantly improved by LIG and SH, yet SI not. Moreover, the expression of TLR4, p-NF-kB p65, TNF-α and IL-6, was significantly downregulated by LIG and SH treatment. So was Prx1 expression and release. CONCLUSIONS: LIG and SH provide the potent neuroprotective effects against hemorrhagic stroke by inhibiting Prx1/TLR4/NF-kB signaling and the subsequent immune and neuroinflammation lesions.
