Gifu Pharmaceutical University

Cerebral infarction is a severe condition that causes motor dysfunction and disorientation due to irreversible neuronal cell death. After an ischemic stroke, the lack of oxygen and nutrients induces cerebral neuronal damage along with mitochondrial dysfunction. Therefore, activating mitochondrial function is a promising strategy for treating ischemic stroke. This study aimed to examine whether Mitochonic acid 5 (MA-5), a compound that targets mitochondria to stimulate ATP synthesis, has protective effects against cerebral ischemia/reperfusion (I/R) injury. We first confirmed that MA-5 significantly increases ATP production after 1 h of exposure to neuron-like cells. MA-5 also increased ATP production coupled respiration in SH-SY5Y cells after the induction of OGD/R. After inducing cerebral I/R in mice via transient midbrain occlusion (t-MCAO), the administration of MA-5 reduced neurological deficits and infarct volume. In addition, MA-5 suppressed the increase in the Bax/Bcl-2 ratio, an index of mitochondria-mediated apoptosis after t-MCAO. Taken together, these results suggest that MA-5 may be a useful therapeutic agent against ischemic stroke by activating mitochondrial function.

The skin plays a critical role in protecting against water loss from the inside and pathogen invasion from the outside. The expression levels and localization of claudin-1 (CLDN1) are responsible for the tight junction (TJ) barrier function in the epidermis. Nonthermal atmospheric pressure plasma (NTAPP) has recently received attention as a novel tool in life sciences, including dermatology. NTAPP application showed useful effects on the skin, including antimicrobial activity, wound healing promotion, and anticancer activity for melanoma. However, it remains unknown how NTAPP indirect irradiation affects skin cells. In this study, we used the human epidermal keratinocyte HaCaT cells to clarify the effect of NTAPP-irradiated medium (PAM) on the epidermal TJ barrier function. Treatment with 30 % of the medium irradiated no distance from NTAPP (PAM0) significantly decreased the expression levels of CLDN1 protein. PAM0 significantly decreased the localization of CLDN1 in the cell-cell contact area. After PAM0 treatment, further culture without PAM0 significantly restored the expression and localization of CLDN1 to the same level as in the control cells. The PAM0-induced changes in protein expression and localization of CLDN1 involve lysosome degradation via a clathrin-dependent endocytosis. Treatment with PAM0 decreases transepithelial electrical resistance and increases the intercellular permeability of low-molecular-weight compounds but not high-molecular-weight compounds. The present study shows that treatment with PAM0 weakens intercellular permeability by decreasing the TJ localization of CLDN1 protein in human epidermal keratinocytes. The technology using NTAPP may be useful to promote transdermal absorption of drugs that are difficult to permeate into the body.