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Preparation of Polyoxometalate-based Photo-responsive Membranes for the Photo-activation of Manganese Oxide Catalysts
Published on: August 7, 2018
Highly amphiphilic manganese porphyrin for the mitochondrial targeting antioxidant
Takayuki Haruyama1, Shoichiro Asayama, Hiroyoshi Kawakami
1Department of Applied Chemistry, Tokyo Metropolitan University, and 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397, Japan.
Abstract:
Here, we communicate that the design of the anti-oxidant consisting of amphiphilic manganese porphyrin with one dimethylimidazolium group and three phenyl groups for mitochondrion targeting. The resulting Mn-porphyrin MnMImP(3)P exhibited high partition coefficient (logP(ow) = +4.78) as well as significant superoxide dismutase and peroxynitrite decomposition activities. Accordingly, the MnMImP(3)P exhibited a little increase in fluorescence intensity attributed to 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide [diS-C(3)-(5)], a tracer dye to assess the mitochondrial membrane potential, which suggested the interaction of the MnMImP(3)P, leading to the release of the fluorescence dye from the mitochondrial membrane, with the mitochondria. As a result, the MnMImP(3)P rescued the cell death under oxidative stress concerned with mitochondrial damage.
Insights
This study introduces a novel manganese porphyrin (MnMImP(3)P) designed for mitochondrion targeting. The antioxidant effectively scavenged reactive oxygen species, protecting cells from oxidative stress and mitochondrial damage.
Area of Science:
- Biochemistry
- Materials Science
- Cell Biology
Background:
- Mitochondrial damage is implicated in various pathologies.
- Antioxidants are crucial for mitigating oxidative stress.
- Targeting mitochondria with therapeutic agents can enhance efficacy.
Purpose of the Study:
- To design and synthesize a novel amphiphilic manganese porphyrin for targeted mitochondrial delivery.
- To evaluate the antioxidant properties and mitochondrial interaction of the synthesized compound.
- To assess the protective effect of the compound against oxidative stress-induced cell death.
Main Methods:
- Synthesis of amphiphilic manganese porphyrin (MnMImP(3)P) with specific functional groups.
- Determination of partition coefficient (logP(ow)) to assess lipophilicity.
- Enzymatic assays for superoxide dismutase and peroxynitrite decomposition activities.
- Mitochondrial membrane potential assessment using a fluorescent dye (diS-C(3)-(5)).
- Cell viability assays under oxidative stress conditions.
Main Results:
- The synthesized Mn-porphyrin, MnMImP(3)P, demonstrated a high partition coefficient (+4.78), indicating good lipophilicity for membrane interaction.
- MnMImP(3)P exhibited significant superoxide dismutase and peroxynitrite decomposition activities.
- The compound interacted with mitochondria, evidenced by the release of the fluorescent dye diS-C(3)-(5) from the mitochondrial membrane.
- MnMImP(3)P effectively rescued cells from death induced by oxidative stress and mitochondrial damage.
Conclusions:
- The novel manganese porphyrin MnMImP(3)P is effectively targeted to mitochondria.
- MnMImP(3)P possesses potent antioxidant capabilities, including superoxide dismutase and peroxynitrite decomposition.
- This mitochondrion-targeted antioxidant demonstrates significant cytoprotective effects against oxidative stress.
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