Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Aug 4

PMID 22860104

Citations 28

Authors

Claudia A Benavente

Stephanie A Schnell

Elaine L Jacobson

Affiliations

Soon will be listed here.

Abstract

Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), NAD(+)-dependent enzymes, link cellular energy status with responses to environmental stresses. Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known etiology in skin cancer. Thus, understanding the defense mechanisms in response to UV, including the role of SIRTs and PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT family members in human skin. SIRTs gene expressions are progressively upregulated in A431 epidermoid carcinoma cells (SIRTs1 and 3), actinic keratoses (SIRTs 2, 3, 5, 6, and 7) and squamous cell carcinoma (SIRTs 1-7). Photodamage induces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases NAD(+), the sirtuin substrate, results in an increase in acetylated proteins, upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT responses to photodamage, abrogation of PARP activation following photodamage, and increased sensitivity to photodamage that is completely reversed by repleting niacin. These data support the hypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamage and may be targets for skin cancer prevention.

Citing Articles

Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD/SIRT1 Pathway.

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Discovery of Novel Thiazole-Based SIRT2 Inhibitors as Anticancer Agents: Molecular Modeling, Chemical Synthesis and Biological Assays.

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Sirtuins Affect Cancer Stem Cells via Epigenetic Regulation of Autophagy.

Sipos F, Muzes G Biomedicines. 2024; 12(2).

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SIRT4 in ageing.

He L, Liu Q, Cheng J, Cao M, Zhang S, Wan X Biogerontology. 2023; 24(3):347-362.

PMID: 37067687 DOI: 10.1007/s10522-023-10022-5.

The role of sirtuins in dermal fibroblast function.

Gilbert M, Mathes S, Mahajan A, Rohan C, Travers J, Thyagarajan A Front Med (Lausanne). 2023; 10:1021908.

PMID: 36993812 PMC: 10040577. DOI: 10.3389/fmed.2023.1021908.

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