title: Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing.
abstract: Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.
authors.affiliation: University of California Irvine, Irvine, California 92612 United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Spitler
authors.affiliation: University of California Irvine, Irvine, California 92612 United States.
authors.forename: Hsiang
authors.initials: H
authors.lastname: Ho
authors.affiliation: University of California Irvine, Irvine, California 92612 United States.
authors.forename: Frederique
authors.initials: F
authors.lastname: Norpetlian
authors.affiliation: University of California Irvine, Irvine, California 92612 United States.
authors.forename: Xiangduo
authors.initials: X
authors.lastname: Kong
authors.affiliation: University of California San Diego, La Jolla, California 92093 United States.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: University of California Irvine, Irvine, California 92612 United States.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yokomori
authors.affiliation: University of California Irvine, Irvine, California 92612 United States.
authors.forename: Bogi
authors.initials: B
authors.lastname: Andersen
authors.affiliation: University of California San Diego, La Jolla, California 92093 United States.
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Boss
authors.affiliation: University of California Irvine, Irvine, California 92612 United StatesbUniversity of California San Diego, La Jolla, California 92093 United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Berns
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003038:Cobamides / Q000737:chemistry*; D003486:Cyanides / Q000737:chemistry; D006152:Cyclic GMP / Q000737:chemistry; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000737:chemistry; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008027:Light; D028022:Low-Level Light Therapy; D009569:Nitric Oxide / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D010101:Oxygen Consumption; D010777:Photochemistry; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D019810:Sodium Azide / Q000737:chemistry; D014945:Wound Healing
chemical_list: D003038:Cobamides; D003486:Cyanides; D017382:Reactive Oxygen Species; C017142:cobinamide; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D003576:Electron Transport Complex IV; D048049:Extracellular Signal-Regulated MAP Kinases; D006152:Cyclic GMP; D009584:Nitrogen