Photodynamic Inactivation of the Sarcoplasmic Reticulum Ca2+‐ATPase by a Ruthenium Polypyridyl Complex Featuring π‐Expansive Ligands DOI Creative Commons
Gina Elena Giacomazzo,

Gloria Mulas,

Ilaria Palchetti

et al.

Bioinorganic Chemistry and Applications, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Sarcoplasmic reticulum Ca 2+ ‐ATPase (SERCA) is a key protein involved in calcium homeostasis and the pivotal role of plethora biological activities makes SERCA powerful target. The intertwining between signalling reactive oxygen species (ROS) has drawn much attention to investigate photodynamic effect that photosensitizers (PSs), prodrugs are light‐activated produce ROS therapy (PDT), pursue on this important However, only limited classes PSs were considered so far, with most them being porphyrin‐based scaffolds, without considering, best our knowledge, family ruthenium(II) polypyridyl complexes (RPCs), which still attracts increasing interest PDT thanks its unique versatile chemical‐physical repertoire. With goal exploring potential arising from considering possible target for highly effective RPC‐based PSs, herein we studied [Ru(dppn) 2 (bpy‐morph)](PF 6 ) (RuPS) (dppn = benzo[ i ]dipyrido[3,2‐ :2′,3′‐ c ]phenazine, bpy‐morph 2,2′‐bipyridine‐4,4′‐diylbis(morpholinomethanone), where two π‐expansive dppn units guarantees high 1 O sensitization ( ϕ Δ 0.54 ± 0.06 CH 3 CN). To aim, solid supported membrane (SSM) biosensing method was employed, equipped LED light λ em 434 nm, 30 W) perform irradiation experiments. Light activation RuPS (10 μM) induced prompt decrease (30%) translocation by SERCA, leading almost complete loss residual current after 15 min (more than 90% decrease). inhibition then evaluated vivo C2C12 myotubes, chosen as model skeletal muscle biology. Upon establishing cellular internalization via confocal microscopy, found enhance cytosolic concentration up 1.5‐fold‐higher thapsigargin, used positive control. Moreover, differentiated phenotype myotubes reverted RuPS, an likely related impaired activity protein.

Language: Английский

Photodynamic Inactivation of the Sarcoplasmic Reticulum Ca2+‐ATPase by a Ruthenium Polypyridyl Complex Featuring π‐Expansive Ligands DOI Creative Commons
Gina Elena Giacomazzo,

Gloria Mulas,

Ilaria Palchetti

et al.

Bioinorganic Chemistry and Applications, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Sarcoplasmic reticulum Ca 2+ ‐ATPase (SERCA) is a key protein involved in calcium homeostasis and the pivotal role of plethora biological activities makes SERCA powerful target. The intertwining between signalling reactive oxygen species (ROS) has drawn much attention to investigate photodynamic effect that photosensitizers (PSs), prodrugs are light‐activated produce ROS therapy (PDT), pursue on this important However, only limited classes PSs were considered so far, with most them being porphyrin‐based scaffolds, without considering, best our knowledge, family ruthenium(II) polypyridyl complexes (RPCs), which still attracts increasing interest PDT thanks its unique versatile chemical‐physical repertoire. With goal exploring potential arising from considering possible target for highly effective RPC‐based PSs, herein we studied [Ru(dppn) 2 (bpy‐morph)](PF 6 ) (RuPS) (dppn = benzo[ i ]dipyrido[3,2‐ :2′,3′‐ c ]phenazine, bpy‐morph 2,2′‐bipyridine‐4,4′‐diylbis(morpholinomethanone), where two π‐expansive dppn units guarantees high 1 O sensitization ( ϕ Δ 0.54 ± 0.06 CH 3 CN). To aim, solid supported membrane (SSM) biosensing method was employed, equipped LED light λ em 434 nm, 30 W) perform irradiation experiments. Light activation RuPS (10 μM) induced prompt decrease (30%) translocation by SERCA, leading almost complete loss residual current after 15 min (more than 90% decrease). inhibition then evaluated vivo C2C12 myotubes, chosen as model skeletal muscle biology. Upon establishing cellular internalization via confocal microscopy, found enhance cytosolic concentration up 1.5‐fold‐higher thapsigargin, used positive control. Moreover, differentiated phenotype myotubes reverted RuPS, an likely related impaired activity protein.

Language: Английский

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