Selective Activation of a TRPC6 Ion Channel Over TRPC3 by Metalated Type-B Polycyclic Polyprenylated Acylphloroglucinols.

Selective modulation of TRPC6 ion channels is a promising therapeutic approach for neurodegenerative diseases and depression. A significant advancement showcases the selective activation of TRPC6 through metalated type-B PPAP, termed . This success stems from 's 1,3-diketone motif facilitating metal coordination.

Angiotensin II-induced hypertension increases the mutant frequency in rat kidney.

Epidemiological studies revealed an increased risk for kidney cancer in hypertensive patients. In many of these patients, the blood pressure regulating renin-angiotensin-aldosterone system (RAAS) is activated. A stimulated RAAS leads to oxidative stress and increases markers of DNA damage, both in vitro and in animal models of hypertension.

Influences of histone deacetylase inhibitors and resveratrol on DNA repair and chromatin compaction.

Accessibility of DNA is a prerequisite for both DNA damage and repair. Therefore, the chromatin structure is expected to have major impact on both processes, with opposite consequences for the stability of the genome. To analyse the influence of chromatin compaction on the generation and repair of various types of DNA modifications, we modulated the global chromatin structure of AS52 Chinese hamster ovary cells and HeLa cells by treatment with either histone deacetylase inhibitors or resveratrol and measured the repair kinetics of (i) pyrimidine dimers induced by ultraviolet B, (ii) oxidised purines generated by photosensitisation and (iii) single-strand breaks induced by H2O2, using an alkaline elution technique.

Study of the mode and efficiency of DNA binding in the damage induced by photoactivated water soluble porphyrins.

We have investigated the DNA binding interactions and in vitro photoactivated DNA damage induced by a neutral water soluble porphyrin derivative 5,10,15,20-tetrakis(2,4,6-trihydroxyphenyl)porphyrin (TTHPP) and its zinc derivative 5,10,15,20-tetrakis(2,4,6-trihydroxyphenyl)porphyrinato zinc(II) (Zn-TTHPP) upon visible light irradiation through various spectroscopic techniques and employing repair endonucleases. These porphyrin derivatives exhibited high affinity toward DNA through groove binding interactions as evidenced through the UV-vis absorption, emission, circular dichroism spectral and viscosity changes. Interestingly, the free base porphyrin derivative, TTHPP generated efficient singlet oxygen mediated DNA damage sensitive to formamidopyrimidine-DNA glycosylase (Fpg protein), when compared with its metal derivative and to the well-known photosensitizer, hematoporphyrin.

Mouse CSB protein is important for gene expression in the presence of a single-strand break in the non-transcribed DNA strand.

CSB protein is required for strand-specific repair of bulky DNA lesions in transcribed genes and mediates transcription recovery after exposure to DNA-damaging agents. We enzymatically generated DNA single-strand breaks (SSBs) with 3'-OH and 5'-phosphate termini in defined positions of a plasmid-borne gene and measured their effect on transcription in cell lines with different statuses of the Csb gene. A single SSB in the transcribed region of the gene caused significant decrease of gene expression.

Photoinduced DNA damage efficiency and cytotoxicity of novel viologen linked pyrene conjugates.

Novel viologen linked pyrene conjugates permeate cells efficiently and exhibit spacer length dependent DNA damage and cytotoxicity upon photoexcitation.

APE1 overexpression in XRCC1-deficient cells complements the defective repair of oxidative single strand breaks but increases genomic instability.

XRCC1 protein is essential for mammalian viability and is required for the efficient repair of single strand breaks (SSBs) and damaged bases in DNA. XRCC1-deficient cells are genetically unstable and sensitive to DNA damaging agents. XRCC1 has no known enzymatic activity and is thought to act as a scaffold protein for both SSB and base excision repair activities.