Inducible Nitric Oxide Synthase/Nitric Oxide System as a Biomarker for Stress and Ease Response in Fish: Implication on Na+ Homeostasis During Hypoxia

Abstract

The cellular and organismal response to stressor-driven stimuli evokes stress response in vertebrates including fishes. Fishes have evolved varied patterns of stress response, including ionosmotic stress response, due to their sensitivity to both intrinsic and extrinsic stimuli. Fishes that experience hypoxia, a detrimental stressor that imposes systemic and cellular stress response, can evoke disturbed ion homeostasis. In addition, like other vertebrates, fishes have also developed mechanisms to recover from the impact of stress by way of shifting stress response into ease response that could reduce the magnitude of stress response with the aid of certain neuroendocrine signals. Nitric oxide (NO) has been identified as a potent molecule that attenuates the impact of ionosmotic stress response in fish, particularly during hypoxia stress. Limited information is, however, available on this important aspect of ion transport physiology that contributes to the mechanistic understanding of survival during environmental challenges. The present review, thus, discusses the role of NO in Na+ homeostasis in fish particularly in stressed conditions. Isoforms of nitric oxide synthase (NOS) are essential for the synthesis and availability of NO at the cellular level. The NOS/NO system, thus, appears as a unique molecular drive that performs both regulatory and integrative mechanisms of control within and across varied fish ionocytes. The activation of the inducible NOS (iNOS)/NO system during hypoxia stress and its action on the dynamics of Na+/K+-ATPase, an active Na+ transporter in fish ionocytes, reveal that the iNOS/NO system controls cellular and systemic Na+ transport in stressed fish. In addition, the higher sensitivity of iNOS to varied physical stressors in fishes and the ability of NO to lower the magnitude of ionosmotic stress in hypoxemic fish clearly put forth NO as an ease-promoting signal molecule in fishes. This further points to the signature role of the iNOS/NO system as a biomarker for stress and ease response in the cycle of adaptive response in fish.

Label-free and TMT-labeled proteomics methods to compare differences on normal liver + extra-celiac liver of Glyptosternum maculatum

“…The activated inducible nitric-oxide synthase (iNOS)/NO in hypoxic sh is favoured for stress adaptation processes to exhibit a cycle of adaptive responses. Fish can rely on the iNOS/NO system to restore basal homeostasis through recovery activities (Peter et al 2022). Hypoxic conditions can lead to brosis of the liver, and HIF-1 signaling worsens the metabolic pro le and hastens nonalcoholic fatty liver disease progression (Mesarwi et al 2021).…”

Nitric Oxide Function and Nitric Oxide Synthase Evolution in Aquatic Chordates

“…The ability of animals to cope with stress-dependent challenges represents a fundamental mechanism for maintaining organism homeostasis. NO is involved, for example, in the teleost response to osmotic stress [ 78 ], hypoxia [ 79 ], and thermal stress [ 80 ].…”

Melatonin integrates multidimensional regulation of Na+/K+-ATPase in ionocytes and promotes stress and ease response in hypoxia-induced air-breathing fish: lessons from integrative approach

“…The branchial ionocytes, popularly known as chloride cells or mitochondrial rich cells, are the integral part of branchial epithelia and act as the major site for ion and water exchange in teleosts ( Evans et al, 2005 ) including zebrafish ( Guh and Hwang, 2017 ) and air-breathing fish ( Rejitha et al, 2009 ; Peter et al, 2011 ). Likewise, renal ionocytes that are located in the proximal, distal and collecting tubules of kidney and the enteric ionocytes in the intestinal epithelia are equally involved in the regulation of systemic Na + homeostasis ( Peter et al, 2022 ). These ionocytes in the osmoregulatory epithelia possess a transmembrane ion transporter NKA that drives electrochemical Na + gradient and membrane potential of cell, contributes to the osmotic regulation of cell volume ( Mobasheri et al, 2000 ) and ion homeostasis ( McCormick, 2001 ; Peter and Gayathry, 2021 ).…”

“…Extensive studies have shown that when kept at water immersion for 30 min this fish underwent hypoxia with a modified regulatory dynamics of NKA at transcriptomic level as evident in the altered pattern of mRNA expression of nkaα1 sub isoforms such as nkaα1a, nkaα1b and nkaα1c in the osmoregulatory tissues ( Simi et al, 2017 ; Peter and Gayathry, 2021 ). It has been documented that upon stressor exposure, fish develops a cycle of adaptive response that produces both stress and ease response ( Peter, 2013 ; Peter et al, 2022 ). With the classic disturbance in physiological mechanisms that include a disturbed ion homeostasis, fishes evoke stress response along with the release of stress hormones such as adrenaline and cortisol ( Wendelaar Bonga, 1997 ).…”

“…With the classic disturbance in physiological mechanisms that include a disturbed ion homeostasis, fishes evoke stress response along with the release of stress hormones such as adrenaline and cortisol ( Wendelaar Bonga, 1997 ). Alternatively, fishes have also developed mechanism to ameliorate the magnitude of stress response by evoking recovery or ease response in order to regain the basal homeostatic status with the aid of neuroendocrine/cytogenic signals like melatonin and nitric oxide ( Peter, 2013 ; Peter and Gayathry, 2021 ; Peter et al, 2022 ). Similarly, beneficial role of melatonin in lowering the magnitude of stress response has been proposed in many fishes ( Sánchez-Vázquez et al, 2019 ; Yang et al, 2021a ; Kruk et al, 2021 ).…”